The S atom from the other NCS− ion completes the distorted square-pyramidal coordination.In the title complex, [Cu(NCS) DOI: 10.1107/S1600536809048594/kj2135Isup2.hklStructure factors: contains datablocks I. DOI:  crystallographic information; 3D view; checkCIF reportAdditional supplementary materials:


In the crystal structure, intermolecular O—H⋯O hydrogen bonds link the molecules into layers parallel to the bc plane.In the title mononuclear complex, [Cu(C DOI: 10.1107/S1600536808010593/cv2398Isup2.hkl            Structure factors: contains datablocks I. DOI:  crystallographic information; 3D view; checkCIF report            Additional supplementary materials:


DOI: 10.1107/S1600536810036202/wm2402Isup2.hkl            Structure factors: contains datablocks I. DOI:  crystallographic information; 3D view; checkCIF report            Additional supplementary materials:


The complete ligand is generated by crystallographic twofold symmetry, resulting in an infinite one-dimensional architecture along [101].In the title coordination polymer, [FeCl DOI: 10.1107/S1600536810002837/hb5310Isup2.hkl            Structure factors: contains datablocks I. DOI:  crystallographic information; 3D view; checkCIF report            Additional supplementary materials:


N—H⋯O hydrogen bonding is present in the crystal structure.In the crystal structure of the title compound, [Cu(C DOI: 10.1107/S1600536809004577/xu2458Isup2.hkl            Structure factors: contains datablocks I. DOI:  crystallographic information; 3D view; checkCIF report            Additional supplementary materials:


The five-membered imidazole ring is disordered over two positions with the major component having a site occupancy of 0.712 (4); the N-bound methyl substituents are ordered. The imidazole ring is approximately perpendicular to the six-membered phenylene ring .The title imidazolium-based ionic-liquid salt, C DOI: 10.1107/S1600536809026324/tk2494Isup2.hkl            Structure factors: contains datablocks I. DOI:  crystallographic information; 3D view; checkCIF report            Additional supplementary materials:


The diethyl ether ligand adopts a nearly planar W-type conformation.In the title compound, [Li(C DOI: 10.1107/S1600536809011556/dn2437Isup2.hkl            Structure factors: contains datablocks I. DOI:  crystallographic information; 3D view; checkCIF report            Additional supplementary materials:


The crystal structure displays weak intermolecular N—H⋯Cl hydrogen bonding.In the title compound, [PdCl DOI: 10.1107/S1600536809008472/rk2132Isup2.hkl            Structure factors: contains datablocks I. DOI:  crystallographic information; 3D view; checkCIF report            Additional supplementary materials:


The NiII ion, lying on an inversion centre, is four-coordinated in a square-planar geometry by two phenolate O and two imine N atoms from two symmetry-related 2-iminomethyl-5-methoxyphenolate ligands. In the crystal, molecules are linked into corrugated layers parallel to (100) by N—H⋯O hydrogen bonds.The title compound, [Ni(C DOI: 10.1107/S1600536809039233/ci2923Isup2.hkl            Structure factors: contains datablocks I. DOI:  crystallographic information; 3D view; checkCIF report            Additional supplementary materials:


DOI: 10.1107/S1600536808023799/tk2286Isup2.hkl            Structure factors: contains datablocks I. DOI:  crystallographic information; 3D view; checkCIF report            Additional supplementary materials:


Correction to: Chiropr Man Therap (2019) 27:63https://doi.org/10.1186/s12998-019-0283-6Original name tagging:After publication of our article  the authAxén IbenHestbaek LiseCorrect name tagging:Leboeuf-Yde CharlotteIben AxénLise HestbaekCharlotte Leboeuf-YdeThe original article has been corrected.


The correct reference is: Salusso A, Raimunda D. Pseudomonas Aeruginosa CDF Transporters CzcD and YiiP are Involved in Zn2+ Efflux, Outer Membrane Permeability and Antibiotic Resistance. Biophys J.; 2017; 112: 3, 16a.


The Pan African Medical Journal. 2018;30:266. doi:10.11604/pamj.2018.30.266.13209.Ce Corrigendum modifie l'article original  Dans l'article original archivé sur Pubmed, le nom de l'auteur Abdelkader Jalil El Hangouche est archivé Hangouche AJE au lieu de El Hangouche AJ .


GigaScience, 6, 2017; doi: 10.1093/gigascience/gix077.A formula was incorrect upon initial publication. The formula “p-value = binomial_cdf (T(v)-Kv(s), T(v), PNull (s))” should instead be “p-value = binomial_cdf (T(v)-Kv(s), T(v), 1-PNull (s)).”This has now been corrected.


Scientific Reports 10.1038/s41598-017-18331-9, published online 21 December 2017Correction to: This Article contains typographical errors in the Acknowledgements section.“Horizon 2020 Framework Programme (H2020) (792720)”should read:“Horizon 2020 Framework Programme (H2020) (732720)”


Nature Communications; 10.1038/ncomms15287; published online 16 May 2017.Correction to: This Article contains errors in Fig.


Correction to: Br J Cancer (2018) 117, 1819–1827; 10.1038/bjc.2017.353; published online 12 October 2017Supplementary Table Supplementary Table 1Supplementary Figure Legends


Scientific Reports5; Article number: 1533810.1038/srep15338; published online: 10212015; updated: 07022018In the original version of this Article, the author Karthiga Santhana Kumar was incorrectly indexed.In addition, this Article contained an error in the Results section, under the subheading ‘Automated quantification of cell dissemination’,http://www.infozentrum.ethz.ch/uploads/user_upload/Software/.”“A program suite referred to as automated Cell Dissemination counter (aCDc) consisting of three open source, executable Java programs (.jar) files can be downloaded through the following web link now reads:https://urldefense.proofpoint.com/v2/url?u=http-3A__www.infozentrum.ethz.ch_uploads_user-5Fupload_Software_ImageAnalysisSoftware.zip&d=DwIGaQ&c=vh6FgFnduejNhPPD0fl_yRaSfZy8CWbWnIf4XJhSqx8&r=Q0HWMVGq_tlDBf7wAxJCv189FbTXBj2Fzg4N_lVZ7NM&m=y4-cT7GLvN-bRkjsbfl2iBNdNwRNEYQ4YmdXP3tZjas&s=o6yob3XKrSnFjEfuAxXQN7WgIuJhyqBCi8hBAm94hFg&e=.”“A program suite referred to as automated Cell Dissemination counter (aCDc) consisting of three open source, executable Java programs (.jar) files can be downloaded through the following web link


This article has been corrected: The correct affiliation information is given below:1 Josep Carreras Leukemia Research Institute, Universitat Autònoma de Barcelona, Spainhttps://doi.org/10.18632/oncotarget.12497Original article: Oncotarget. 2016; 7:72057-72066.


Scientific Reports 10.1038/s41598-017-06977-4, published online 08 August 2017Correction to: This Article contained an error in the legend of Table 1 where,“For each interactors, the interacting TANC protein, the detection method and the binding region  are here listed. Y2H: Yeast two hybrid; Co-IP: Co-immunoprecipitation; SPR: Surface plasmon resonance HTS: High-Throughput System; AC: Affinity Capture; PL: Proximity Label; MS: Mass spectrometry; CLIP: Cross-Linking ImmunoPrecipitation SF-TAP/MS: systematic tandem affinity purifications coupled to mass spectrometry. LIG_PDZ_Class_1: PDZ-binding motif; LIG_EVH1_1: Proline-rich motif binding to signal transduction class I EVH1 domains; DEG_SCF_TRCP1: SCF-betaTrCP1 complex target site; MOD_LATS_1: phosphorylation motif recognised by the LATS kinases; DOC_PP1_RVXF_1: PP1 docking motif; LIG_14-3-3_2: phospho-motif mediating the interaction with 14-3-3 proteins; LIG_Actin_WH2_2: Actin-binding motif; TRG_NES_CRM1_1: Nuclear Export Signal.”now reads:3) and helium (0.03 g/cm3) were kept fixed during the fitting procedure, and their thicknesses were infinite. Error estimates were obtained for every parameter by varying the parameter until the χ based R-value is changed by 5% . The method does not reveal correlations between the parameters. On the right side, theoretical bulk density and the molecular length of the molecules are given for comparison.”“The tabulated parameters are obtained from fitting the reflectivity data with box models. For models with more than one layer, the layer closest to the calcite surface is indexed 1 (e.g. Methanol-1). The density for calcite (2.71 g/cm


G. Tuberoso.


Scientific Data 2:150050 doi: 10.1038/sdata.2015.50 (2015); Published 29 September 2015; Updated 3 July 2018.Panels a-e were accidentally omitted from


Correction to: BMC Genomics (2019) 20:262https://doi.org/10.1186/s12864-019-5576-6Following publication of the original article , the autPamponét Vanessa Carvalho CayresOriginally the author name was published as:Vanessa Carvalho Cayres PamponétThe correct author name is:


The European Centre for Disease Prevention and Control (ECDC) invites applications for the following positions:Disease Programme Coordination ManagerThe application deadline expires on 03 September 2018. Financial assistantThe application deadline expires on 03 September 2018.https://ecdc.europa.eu/en/work-us/vacancies?f%5B0%5D=deadline_date%3A1&f%5B1%5D=vacancy_type%3A1700For more information on either position, please visit the ECDC website:


The original publication  containsThe correct version:Medina-Pradas et al. (2011): “EFA/CV/CtV/ICR”


Pulmonaria officinalis L., Boraginaceae) is considered to possess therapeutic properties and it has been traditionally used as a remedy against various lung disorders in many countries. Nevertheless, very few data concerning its phytochemical composition are available. This research aims to provide a detailed description of specialized metabolites from the aerial parts of lungwort. Nine previously undescribed and 36 known phenolic compounds were detected in the 50% methanolic extract. Following multistep preparative procedures, structures of newly discovered compounds were determined using one- and two-dimensional techniques of NMR spectroscopy. Among the identified compounds were caffeic acid esters with aliphatic hydroxycarboxylic acids, conjugates of dicaffeic acid with rosmarinic acid, and previously unknown isomers of isosalvianolic acid A and yunnaneic acid E, as well as other lignans. Concentrations of all identified phenolic derivatives in the investigated herbal material were estimated using a method based on liquid chromatography with high-resolution mass spectrometry detection. Seasonal changes in the concentration of metabolites were also investigated using targeted and untargeted metabolomics techniques.Lungwort ( Pulmonaria officinalis L (lungwort), belonging to the Boraginaceae family, is a herbaceous perennial plant, widely spread in Europe and western Asia. It has a long tradition of use in folk medicine of many countries as a remedy against various respiratory diseases including asthma, chronic bronchitis, tuberculosis, laryngitis, and coughs. It also has expectorant, antitussive, and diaphoretic properties  photocycloaddition of two olefinic moieties − at m/z 353. Compound 6 was identified as 3-O-caffeoylquinic acid, whereas compound 9 was identified as 4-O-caffeoylquinic acid, by comparisons of MS/MS fragmentation patterns and retention times with that of authentic standards. The last isomer was only tentatively identified as a 5-O-caffeoylquinic acid (13) by its fragmentation pattern alone − ion of digoxin at RT 17.48 min). At this stage of data processing, standard t-test and fold-change analyses were carried out to provide a preliminary overview of features potentially characteristic for the two phenological stages under study. Next, all missing intensity values and intensities that were equal to zero in the data matrix were replaced by the half of the minimum positive value that was found within the data, and multivariate PCA was applied to investigate systematic variation in the data matrix and to identify potential groups in an unsupervised manner.For untargeted metabolomic analyses, data obtained from LC-QTOF-MS/MS runs were processed using Find Molecular Features function of Bruker DataAnalysis ver. 4.4 SR1 software. The following parameters were used: a signal-to-noise threshold of 9, correlation coefficient threshold of 0.7, and the minimum compound length of seven spectra. For each detected compound, in addition to the deprotonated ion, all typical adduct and composite ions were grouped into a single feature. Next, features from the entire dataset were subjected to advanced bucket generation with Bruker ProfileAnalysis ver. 2.3 software, using retention time range 1.2–22.0 min and oAnalyst . Data weThe bias related to instrumental drift was minimized by randomization of the sample list injection order. It was achieved using an in-house-developed VBA  script in Microsoft Excel.P. officinalis that had been isolated in the course of this study, and 25 µg/mL of the internal standard. This QC sample was used to monitor the quality and stability of the data acquisition and was analyzed in replicate after each block of 20 analyses.The performance of the LC-MS and the data processing systems were monitored with two types of quality control (QC) samples. Class-specific QC samples  were prepared by mixing 10 µL aliquots of each sample within the group and diluting them 10 times, just like normal samples. Class QC samples were analyzed after every six analyses of normal samples. During data processing, features detected in less than 75% of class-specific QC samples were removed from the dataset. The frequency distribution of the relative standard deviation for the peak intensities and peak numbers in the QC samples are given in 1H, 13C DEPTQ, 1H–13C HSQC, 1H–13C H2BC, 1H–13C HMBC, 1H–13C F2-coupled perfect-CLIP HSQC, 1H–13C HSQC-TOCSY, 1H–1H COSY DQF, 1H–1H TOCSY, 1H–1H NOESY, 1H–1H TROESY, 1D–TOCSY, 1D-TROESY, CSSF-1D-NOESY, and CSSF-1D-TOCSY − .Danshensu  lactic acid (2); light brownish amorphous powder; UV  λmax (nm) 260; HR-QTOF-MS (neg.) m/z 312.1086 [M − H]− .Menisdaurin (O-(E)-Caffeoyl-threonic acid (3); white amorphous powder; UV  λmax (nm) 325; −5 M, MeOH): [Θ]228 − 3330, [Θ]252 − 32, [Θ]259 − 170, [Θ]297 + 2385, [Θ]306 + 2250, [Θ]315 + 1877, [Θ]322 + 2185, [Θ]325 + 2034, [Θ]333 + 2338, [Θ]342 + 1962, [Θ]347 + 2091, [Θ]372 + 284, [Θ]377 + 340; HR-QTOF-MS (neg.) m/z 297.0619 [M − H]− . 1H and 13C-NMR spectroscopic data (3-pic data .O-(E)-Caffeoyl-l-threonic acid (4); white amorphous powder; UV  λmax (nm) 325; −5 M, MeOH) [Θ]237 + 1647, [Θ]338 − 1574; HR-QTOF-MS (neg.) m/z 297.0611 [M − H]− .2-5); white amorphous powder; UV  λmax (nm) 275; HR-QTOF-MS (neg.) m/z 215.0825 [M − H]− .Lycoperodine-1 (6); white amorphous powder; UV  λmax (nm) 325; HR-QTOF-MS (neg.) m/z 353.0882 [M − H]− .Chlorogenic acid (7); white amorphous powder; UV  λmax (nm) 325; HR-QTOF-MS (neg.) m/z 405.2126 [M − H]− .Actinidioionoside (8); white amorphous powder; UV  λmax (nm) 325; HR-QTOF-MS (neg.) m/z 179.0262 [M − H]− .Caffeic acid (9); white amorphous powder; UV  λmax (nm) 325; HR-QTOF-MS (neg.) m/z 353.0882 [M − H]− .Cryptochlorogenic acid (O-(E)-Feruloyl-α-sorbopyranosyl-(2′→1)-α-glucopyranoside (10); white amorphous powder; UV  λmax (nm) 325; m/z 517.1572 [M − H]− . 1H and 13C-NMR spectroscopic data (3′-pic data .O-(E)-Caffeoyl-d-glyceric acid (11); white amorphous powder; UV  λmax (nm) 325; −5 M, MeOH) [Θ]265 − 144, [Θ]317 − 5806, [Θ]380 + 296; HR-QTOF-MS (neg.) m/z 267.0508 [M − H]− .2-O-(E)-Caffeoyl-l-threonic acid (12); white amorphous powder; UV  λmax (nm) 215, 325; −5 M, MeOH) [Θ]261−169, [Θ]283 − 593, [Θ]300 − 509, [Θ]325 − 1349, [Θ]384 + 80, [Θ]380 + 296; HR-QTOF-MS (neg.) m/z 297.0616 [M − H]− .4-13); tentative identification; UV  λmax (nm) 325; HR-QTOF-MS (neg.) m/z 353.0878 [M − H]− .Neochlorogenic acid (O-(E)-Caffeoyl- glyceric acid (14); white amorphous powder; UV  λmax (nm) 215, 325; −5 M, MeOH) [Θ]231 − 1125, [Θ]253 − 207, [Θ]273 − 277, [Θ]293 + 208, [Θ]305 + 429, [Θ]324 + 1234, [Θ]343 + 76, [Θ]358 − 204, [Θ]373 − 286; HR-QTOF-MS (neg.) m/z 267.0509 [M − H]− .1H and 13C-NMR spectroscopic data (3-pic data . O-p-Coumaroylquinic acid (15); white amorphous powder; UV  λmax (nm) 225, 310; m/z 337.0924 [M − H]− .3-O-p-Coumaroylquinic acid (16); tentative identification; UV  λmax (nm) 225, 310; HR-QTOF-MS (neg.) m/z 337.0926 [M − H]− .4-O-p-Coumaroylquinic acid (17); tentative identification; UV  λmax (nm) 225, 310; HR-QTOF-MS (neg.) m/z 337.0924 [M − H]− .5-18); white amorphous powder; UV  λmax (nm) 255, 345; −5 M, MeOH) [Θ]254 − 14186, [Θ]292 + 3337, [Θ]313 − 4443, [Θ]351 + 12263; HR-QTOF-MS (neg.) m/z 537.1034 [M − H]− . 1H and 13C-NMR spectroscopic data (Globoidnan B (pic data .19) yellow amorphous powder; UV  λmax (nm) 255, 355; HR-QTOF-MS (neg.) m/z 609.1464 [M − H]− .Rutin (20); tentative identification; UV  λmax (nm) 345; HR-QTOF-MS (neg.) m/z 593.1501 [M − H]− .Nicotiflorin isomer (O-β-glucoside (21); yellow amorphous powder; UV  λmax (nm) 255, 355; HR-QTOF-MS (neg.) m/z 463.0892 [M − H]− .Quercetin 3-22); white amorphous powder; UV  λmax (nm) 265; m/z 571.1092 [M − H]− .Yunnaneic acid E -β-glucoside (23); yellow amorphous powder; UV  λmax (nm) 255, 355; HR-QTOF-MS (neg.) m/z 549.0876 [M − H]− .Quercetin 3-24); yellow amorphous powder; UV  λmax (nm) 265, 345; HR-QTOF-MS (neg.) m/z 593.1503 [M − H]− .Nicotiflorin (25); yellow amorphous powder; UV  λmax (nm) 265, 345; HR-QTOF-MS (neg.) m/z 447.0940 [M − H]− .Astragalin (26); light cream amorphous powder; UV  λmax (nm) 285; HR-QTOF-MS (neg.) m/z 719.1607 [M − H]− .Shimobashiric acid C (27); light yellowish amorphous powder; UV  λmax (nm) 220, 330; CD  [Θ]232 − 9423, [Θ]254 − 1004, [Θ]275 − 3233, [Θ]302 + 7406, [Θ]313 + 6634, [Θ]326 + 7255; HR-QTOF-MS (neg.) m/z 359.0773 [M − H]− .Rosmarinic acid -β-glucoside (28); yellow amorphous powder; UV  λmax (nm) 265, 345; HR-QTOF-MS (neg.) m/z 533.0940 [M − H]− .Kaempferol 3-29); white amorphous powder; UV  λmax (nm) 310; −5 M, MeOH) [Θ]253 − 70887, [Θ]290 + 6650, [Θ]332 − 7130, [Θ]386 + 290; HR-QTOF-MS (neg.) m/z 537.1035 [M − H]− .Monardic acid A (30); white amorphous powder; UV  λmax (nm) 265; HR-QTOF-MS (neg.) m/z 509.1094 [M − H]− . 1H and 13C-NMR spectroscopic data -2-((3-(3-(carboxycarbonyl)-3′,4′-dihydroxy--4-yl) propanoyl)oxy)-3-propanoic acid (pic data .31); white amorphous powder; UV  λmax (nm) 310; −5 M, MeOH) [Θ]253 + 28451, [Θ]281 − 3444, [Θ]330 + 8800; HR-QTOF-MS (neg.) m/z 537.1054 [M − H]− .Lithospermic acid A (32); white amorphous powder; UV  λmax (nm) 325; −5 M, MeOH) [Θ]237 + 16506, [Θ]246 + 15155, [Θ]253 + 15786, [Θ]247 − 4592, [Θ]294 + 15809, [Θ]341 − 47198; HR-QTOF-MS (neg.) m/z 999.2766 [M − H]− . 1H and 13C-NMR spectroscopic data (Pulmonarioside A (pic data .O-(8″-Z-caffeoyl) rosmarinic acid) (33); white amorphous powder; UV  λmax (nm) 325; m/z 537.1034 [M − H]− .Salvianolic acid H, (3′-34); white amorphous powder; UV  λmax (nm) 250; 288; 330; −5 M, MeOH) [Θ]235 + 14042, [Θ]255 + 25042, [Θ]280 − 2869; [Θ]303 + 9014, [Θ]334 + 11379; HR-QTOF-MS (neg.) m/z 717.1444 [M − H]− .Lithospermic acid B (35); white amorphous powder; UV  λmax (nm) 325; −5 M, MeOH) [Θ]253 + 32447, [Θ]274 − 4384, [Θ]296 + 20685, [Θ]340 − 56660; HR-QTOF-MS (neg.) m/z 1013.2946 [M − H]− . 1H and 13C-NMR spectroscopic data (Pulmonarioside B (pic data .36); white amorphous powder; UV  λmax (nm) 280; −5 M, MeOH) [Θ]231 − 13436, [Θ]252 − 9737, [Θ]269 − 11309, [Θ]300 + 41370; HR-QTOF-MS (neg.) m/z 1093.2255 [M − H]− .Yunnaneic acid B (37); white amorphous powder; UV  λmax (nm) 260, 320; m/z 491.0979 [M − H]− .Globoidnan A (38); white amorphous powder; UV  λmax (nm) 325; −5 M, MeOH) [Θ]246 + 10304, [Θ]284 − 24134, [Θ]324 + 26434; HR-QTOF-MS (neg.) m/z 551.1190 [M − H]− .1H and 13C-NMR spectroscopic data (Pulmitric acid A (pic data .39); white amorphous powder; UV  λmax (nm) 320; m/z 535.0885 [M − H]− ; 1H and 13C-NMR spectroscopic data (Pulmitric acid B (pic data .40); white amorphous powder; UV  λmax (nm) 320; −5 M , MeOH) [Θ]230 − 7505, [Θ]255 + 5772, [Θ]276 − 1307, [Θ]305 + 15195; HR-QTOF-MS (neg.) m/z 493.1134 [M − H]− ; 1H and 13C-NMR spectroscopic data ; white amorphous powder; UV  λmax (nm) 320; −5 M, MeOH) [Θ]248 − 6367, [Θ]305 + 3958; HR-QTOF-MS (neg.) m/z 493.1134 [M − H]− ; 1H and 13C-NMR spectroscopic data ; tentative identification; UV  λmax (nm) 320; HR-QTOF-MS (neg.) m/z 493.1133 [M − H]− .Isosalvianolic acid A isomer (43); white amorphous powder; UV  λmax (nm) 330; m/z 373.0932 [M − H]− . Rosmarinic acid methyl ester (44); white amorphous powder; UV  λmax (nm) 325; HR-QTOF-MS (neg.) m/z 551.1189 [M − H]− . Salvianolic acid H-9″-methylester (3′-O-(8″-Z-caffeoyl)rosmarinic acid-9″-methylester) (45) tentative identification; UV  λmax (nm) 220; HR-QTOF-MS (neg.) m/z 519.0926 [M − H]− .Lycopic acid C (Pulmonaria officinalis. The presented research may provide insights for the potential applications of lungwort as a dietary supplement or a nutraceutical, and may it also contribute to the broader application of Pulmonariae Herba. Extracts of P. officinalis may serve as a prominent supply of rosmarinic acid and related compounds, as well as a source of several others metabolites. Among the 45 identified metabolites, we found many compounds with well-established therapeutic properties, although none of them alone can be directly associated with the ethnomedicinal use of lungwort. Our results also show progressive changes in the phytochemical composition of P. officinalis during the phenological cycle, presumably reflecting both changes in the physiological state of plants, as well as varying intensity of different abiotic factors.To the best of our knowledge, this is the first comprehensive study of specialized metabolites in the aerial parts of


Chem. Commun., 2018, DOI: 10.1039/c7md00575j.Correction for ‘Novel valdecoxib derivatives by ruthenium(


Retraction Note: Stem Cell Res Therhttps://doi.org/10.1186/scrt443This article  has been


Correction to: Antimicrob Resist Infect Controlhttps://doi.org/10.1186/s13756-018-0389-yThe original article  contains“TPB has been employed extensively in pharmacy practice research.”


Enterobacteriaceae, which they named Edwardsiella (for CDC microbiologist Philip R. Edwards) tarda   . These o


This article has been corrected: The correct Title information is given below:ARF–Mdm2–P53-dependent cellular senescenceNLRP6 targeting suppresses gastric tumorigenesis via P14111597-111607. https://doi.org/10.18632/oncotarget.22876Original article: Oncotarget. 2017; 8:


EGFR mediates LPA‐induced proteolytic enzyme expression and ovarian cancer invasion: Inhibition by resveratrol. Mol Oncol7, 121–129.23127547


Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point‐in‐time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.14747. In addition to this overview, in which are identified Other protein targets which fall outside of the subsequent categorisation, there are six areas of focus: G protein‐coupled receptors, ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid‐2019, and supersedes data presented in the 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC‐IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands ( Thyroid hormone receptorsS231 1B. Retinoic acid receptorsS232 1C. Peroxisome proliferator‐activated receptorsS233 1D. Rev‐Erb receptorsS234 1F. Retinoic acid‐related orphansS234 1H. Liver X receptor‐like receptorsS235 1I. Vitamin D receptor‐like receptorsS236 2A. Hepatocyte nuclear factor‐4 receptorsS237 2B. Retinoid X receptorsS238 2C. Testicular receptorsS238 2E. Tailless‐like receptorsS239 2F. COUP‐TF‐like receptorsS239 3B. Estrogen‐related receptorsS240 4A. Nerve growth factor IB‐like receptorsS241 5A. Fushi tarazu F1‐like receptorsS241 6A. Germ cell nuclear factor receptorsS242 0B. DAX‐like receptorsS242 Steroid hormone receptorsS243 3A. Estrogen receptorsS244 3C. 3‐Ketosteroid receptorsS248 Cytokine receptor familyS249 IL‐2 receptor familyS251 IL‐3 receptor familyS252 IL‐6 receptor familyS254 IL‐12 receptor familyS255 Prolactin receptor familyS256 Interferon receptor familyS257 IL‐10 receptor familyS258 Immunoglobulin‐like family of IL‐1 receptorsS259 IL‐17 receptor familyS259 GDNF receptor familyS260 IntegrinsS264 Pattern recognition receptorsS264 Toll‐like receptor familyS266 NOD‐like receptor familyS268 RIG‐I‐like receptor familyS269 Receptor Guanylyl Cyclase (RGC) familyS269 Transmembrane quanylyl cyclasesS270 Nitric oxide (NO)‐sensitive (soluble) guanylyl cyclaseS271 Receptor tyrosine kinases (RTKs)S272 Type I RTKs: ErbB  receptor familyS273 Type II RTKs: Insulin receptor familyS274 Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor familyS275 Type IV RTKs: VEGF  receptor familyS275 Type V RTKs: FGF (broblast growth factor) receptor familyS276 Type VI RTKs: PTK7/CCK4S277 Type VII RTKs: Neurotrophin receptor/Trk familyS278 Type VIII RTKs: ROR familyS278 Type IX RTKs: MuSKS279 Type X RTKs: HGF (hepatocyte growth factor) receptor familyS279 Type XI RTKs: TAM  receptor familyS280 Type XII RTKs: TIE family of angiopoietin receptorsS280 Type XIII RTKs: Ephrin receptor familyS281 Type XIV RTKs: RETS282 Type XV RTKs: RYKS282 Type XVI RTKs: DDR (collagen receptor) familyS283 Type XVII RTKs: ROS receptorsS283 Type XVIII RTKs: LMR familyS284 Type XIX RTKs: Leukocyte tyrosine kinase (LTK) receptor familyS284 Type XX RTKs: STYK1S286 Receptor serine/threonine kinase (RSTK) familyS286 Type I receptor serine/threonine kinasesS287 Type II receptor serine/threonine kinasesS287 Type III receptor serine/threonine kinasesS287 RSTK functional heteromersS289 Receptor tyrosine phosphatase (RTP) familyS291 Tumour necrosis factor (TNF) receptor familyS301 Acetylcholine turnoverS302 Adenosine turnoverS303 Amino acid hydroxylasesS304 L‐Arginine turnoverS304 2.1.1.‐ Protein arginine N‐methyltransferasesS305 ArginaseS305 Arginine:glycine amidinotransferaseS305 Dimethylarginine dimethylaminohydrolasesS306 Nitric oxide synthasesS307 Carbonic anhydrasesS308 Carboxylases and decarboxylasesS308 CarboxylasesS309 DecarboxylasesS311 Catecholamine turnoverS313 Ceramide turnoverS313 Serine palmitoyltransferaseS314 Ceramide synthase4‐desaturaseS314 Sphingolipid ΔS315 Sphingomyelin synthaseS315 Sphingomyelin phosphodiesteraseS316 Neutral sphingomyelinase coupling factorsS316 Ceramide glucosyltransferaseS316 Acid ceramidaseS317 Neutral ceramidasesS317 Alkaline ceramidasesS318 Ceramide kinaseS319 Chromatin modifying enzymesS319 2.1.1.‐ Protein arginine N‐methyltransferasesS320 3.5.1.‐ Histone deacetylases (HDACs)S321 Cyclic nucleotide turnover/signallingS321 Adenylyl cyclases (ACs)S323 Exchange protein activated by cyclic AMP (EPACs)S323 Phosphodiesterases, 3’,5’‐cyclic nucleotide (PDEs)S327 Cytochrome P450S327 CYP2 familyS328 CYP2 familyS329 CYP3 familyS330 CYP4 familyS331 CYP5, CYP7 and CYP8 familiesS332 CYP11, CYP17, CYP19, CYP20 and CYP21 familiesS333 CYP24, CYP26 and CYP27 familiesS333 CYP39, CYP46 and CYP51 familiesS334 DNA topoisomerasesS335 Endocannabinoid turnoverN‐Acylethanolamine turnoverS336 S337 2‐Acylglycerol ester turnoverS338 Eicosanoid turnoverS338 CyclooxygenaseS339 Prostaglandin synthasesS341 LipoxygenasesS342 Leukotriene and lipoxin metabolismS343 GABA turnoverS344 Glycerophospholipid turnoverS345 Phosphoinositide‐specific phospholipase C2S346 Phospholipase AS348 Phosphatidylcholine‐specific phospholipase DS349 Lipid phosphate phosphatasesS349 Phosphatidylinositol kinasesS350 1‐phosphatidylinositol 4‐kinase familyS351 Phosphatidylinositol‐4‐phosphate 3‐kinase familyS351 Phosphatidylinositol 3‐kinase familyS351 Phosphatidylinositol‐4,5‐bisphosphate 3‐kinase familyS352 1‐phosphatidylinositol‐3‐phosphate 5‐kinase familyS353 Type I PIP kinases (1‐phosphatidylinositol‐4‐phosphate 5‐kinase family)S353 Type II PIP kinases (1‐phosphatidylinositol‐5‐phosphate 4‐kinase family)S356 Phosphatidylinositol phosphate kinasesS356 Haem oxygenaseS358 Hydrogen sulphide synthesisS358 HydrolasesS360 Inositol phosphate turnoverS360 Inositol 1,4,5‐trisphosphate 3‐kinasesS360 Inositol polyphosphate phosphatasesS361 Inositol monophosphataseS361 Kinases (EC 2.7.x.x)S362 Rho kinaseS362 Protein kinase C (PKC) familyS363 Alpha subfamilyS363 Delta subfamilyS364 Eta subfamilyS364 FRAP subfamilyS365 Cyclin‐dependent kinase (CDK) familyS365 CDK4 subfamilyS366 GSK subfamilyS367 Polo‐like kinase (PLK) familyS367 STE7 familyS368 Abl familyS368 Ack familyS369 Janus kinase (JakA) familyS369 Src familyS370 Tec familyS371 RAF familyS372 Lanosterol biosynthesis pathwayS374 Nucleoside synthesis and metabolismS376 Paraoxonase (PON) familyS377 Peptidases and proteinasesS377 A1: PepsinS377 A22: PresenilinS378 C14: CaspaseS378 M1: Aminopeptidase NS379 M2: Angiotensin‐converting (ACE and ACE2)S379 M10: Matrix metallopeptidaseS380 M12: Astacin/AdamalysinS380 M28: Aminopeptidase YS381 M19: Membrane dipeptidaseS381 S1: ChymotrypsinS382 T1: ProteasomeS382 S8: SubtilisinS383 S9: Prolyl oligopeptidaseS383 Poly ADP‐ribose polymerasesS384 Prolyl hydroxylasesS384 Sphingosine 1‐phosphate turnoverS385 Sphingosine kinaseS386 Sphingosine 1‐phosphate phosphataseS387 Sphingosine 1‐phosphate lyaseS387 Thyroid hormone turnoverS388 1.14.13.9 Kynurenine 3‐monooxygenaseS389 2.5.1.58 Protein farnesyltransferaseS390 3.5.1.‐ Histone deacetylases (HDACs)S391 3.5.3.15 Peptidyl arginine deiminases (PADI)S391 3.6.5.2 Small monomeric GTPasesS391 RAS subfamilyS392 RAB subfamilyS399 ATP‐binding cassette transporter familyS399 ABCA subfamilyS401 ABCB subfamilyS403 ABCC subfamilyS404 ABCD subfamily of peroxisomal ABC transportersS405 ABCG subfamilyS406 F‐type and V‐type ATPasesS406 F‐type ATPaseS407 V‐type ATPaseS407 P‐type ATPases+/K+‐ATPasesS407 Na2+‐ATPasesS408 Ca+/K+‐ATPasesS408 H+‐ATPasesS408 CuS409 Phospholipid‐transporting ATPasesS409 SLC superfamily of solute carriersS410 SLC1 family of amino acid transportersS410 Glutamate transporter subfamilyS412 Alanine/serine/cysteine transporter subfamilyS413 SLC2 family of hexose and sugar alcohol transportersS413 Class I transportersS414 Class II transportersS415 Proton‐coupled inositol transporterS415 SLC3 and SLC7 families of heteromeric amino acid transporters (HATs)S415 SLC3 familyS416 SLC7 familyS417 SLC4 family of bicarbonate transportersS417 Anion exchangers3− transportersS418 Sodium‐dependent HCOS418 SLC5 family of sodium‐dependent glucose transportersS419 Hexose transporter familyS420 Choline transporterS421 Sodium iodide symporter, sodium‐dependent multivitamin transporter and sodium‐coupled monocarboxylate transportersmyo‐inositol cotransporter transportersS422 Sodium S423 SLC6 neurotransmitter transporter familyS423 Monoamine transporter subfamilyS424 GABA transporter subfamilyS425 Glycine transporter subfamilyS427 Neutral amino acid transporter subfamilyS428 SLC8 family of sodium/calcium exchangersS429 SLC9 family of sodium/hydrogen exchangersS429 SLC10 family of sodium‐bile acid co‐transportersS431 SLC11 family of proton‐coupled metal ion transportersS431 SLC12 family of cation‐coupled chloride transportersS433 SLC13 family of sodium‐dependent sulphate/carboxylate transportersS434 SLC14 family of facilitative urea transportersS435 SLC15 family of peptide transportersS437 SLC16 family of monocarboxylate transportersS438 SLC17 phosphate and organic anion transporter familyS438 Type I sodium‐phosphate co‐transportersS439 Sialic acid transporterS439 Vesicular glutamate transporters (VGLUTs)S440 Vesicular nucleotide transporterS440 SLC18 family of vesicular amine transportersS442 SLC19 family of vitamin transportersS443 SLC20 family of sodium‐dependent phosphate transportersS443 SLC22 family of organic cation and anion transportersS444 Organic cation transporters (OCT)S445 Organic zwitterions/cation transporters (OCTN)S446 Organic anion transporters (OATs)S446 Urate transporterS447 Atypical SLC22B subfamilyS448 SLC23 family of ascorbic acid transportersS449 SLC24 family of sodium/potassium/calcium exchangersS450 SLC25 family of mitochondrial transportersS450 Mitochondrial di‐ and tri‐carboxylic acid transporter subfamilyS451 Mitochondrial amino acid transporter subfamilyS452 Mitochondrial phosphate transportersS452 Mitochondrial nucleotide transporter subfamilyS453 Mitochondrial uncoupling proteinsS454 Miscellaneous SLC25 mitochondrial transportersS454 SLC26 family of anion exchangersS454 Selective sulphate transportersS455 Chloride/bicarbonate exchangersS455 Anion channelsS456 Other SLC26 anion exchangersS457 SLC27 family of fatty acid transportersS458 SLC28 and SLC29 families of nucleoside transportersS458 SLC28 familyS459 SLC29 familyS461 SLC30 zinc transporter familyS461 SLC31 family of copper transportersS462 SLC32 vesicular inhibitory amino acid transporterS463 SLC33 acetylCoA transporterS464 SLC34 family of sodium phosphate co‐transportersS465 SLC35 family of nucleotide sugar transportersS466 SLC36 family of proton‐coupled amino acid transportersS468 SLC37 family of phosphosugar/phosphate exchangersS468 SLC38 family of sodium‐dependent neutral amino acid transportersS469 System A‐like transportersS469 System N‐like transportersS470 Orphan SLC38 transportersS470 SLC39 family of metal ion transportersS471 SLC40 iron transporterS472 SLC41 family of divalent cation transportersS473 SLC42 family of Rhesus glycoprotein ammoniumtransportersS473 SLC43 family of large neutral amino acid transportersS474 SLC44 choline transporter‐like familyS475 SLC45 family of putative sugar transportersS475 SLC46 family of folate transportersS477 SLC47 family of multidrug and toxin extrusion transportersS477 SLC48 heme transporterS478 SLC49 family of FLVCR‐related heme transportersS479 SLC50 sugar transporterS479 SLC51 family of steroid‐derived molecule transportersS480 SLC52 family of riboflavin transportersS481 SLC53 Phosphate carriersS481 SLC54 Mitochondrial pyruvate carriersS482 SLC55 Mitochondrial cation/proton exchangersS482 SLC56 SideroflexinsS483 SLC57 NiPA‐like magnesium transporter familyS483 SLC58 MagT‐like magnesium transporter familyS484 SLC59 Sodium‐dependent lysophosphatidylcholine symporter familyS484 SLC60 Glucose transportersS485 SLC61 Molybdate transporter familyS485 SLC62 Pyrophosphate transportersS486 SLC63 Sphingosine phosphate transportersS486 SLC64 Golgi Ca2+/H+ exchangersS487 SLC65 NPC‐type cholesterol transportersS488 SLCO family of organic anion transporting polypeptideshttps://www.guidetopharmacology.org/). This database is supported by the British Pharmacological Society (BPS), the International Union of Basic and Clinical Pharmacology (IUPHAR), the University of Edinburgh and previously the Wellcome Trust. Data included in the Guide to PHARMACOLOGY are derived in large part from interactions with the subcommittees of the Nomenclature Committee of the International Union of Basic and Clinical Pharmacology (NC‐IUPHAR). A major influence on the development of the database was Tony Harmar (1951‐2014), who worked with a passion to establish the curators as a team of highly informed and informative individuals, with a focus on high‐quality data input, ensuring a suitably validated dataset. The Editors of the Concise Guide have compiled the individual records, in concert with the team of Curators, drawing on the expert knowledge of these latter subcommittees. The tables allow an indication of the status of the nomenclature for the group of targets listed, usually previously published in Pharmacological Reviews. In the absence of an established subcommittee, advice from several prominent, independent experts has generally been obtained to produce an authoritative consensus on nomenclature, which attempts to fit in within the general guidelines from NC‐IUPHAR. This current edition, the Concise Guide to PHARMACOLOGY 2019/20, is the latest snapshot of the database in print form, following on from the Concise Guide to PHARMACOLOGY 2017/18. It contains data drawn from the online database as a rapid overview of the major pharmacological targets. Thus, there are many fewer targets presented in the Concise Guide compared to the online database. The priority for inclusion in the Concise Guide is the presence of quantitative pharmacological data for human proteins. This means that often orphan family members are not presented in the Concise Guide, although structural information is available on the online database. The organisation of the data is tabular (where appropriate) with a standardised format, where possible on a single page, intended to aid understanding of, and comparison within, a particular target group. The Concise Guide is intended as an initial resource, with links to additional reviews and resources for greater depth and information. Pharmacological and structural data focus primarily on human gene products, wherever possible, with links to HGNC gene nomenclature and UniProt IDs. In a few cases, where data from human proteins are limited, data from other species are indicated. Pharmacological tools listed are prioritised on the basis of selectivity and availability. That is, agents  are included where they are both available  AND the most selective. The Concise Guide is divided into seven sections, which comprise pharmacological targets of similar structure/function. These are G protein‐coupled receptors, ion channels , catalytic receptors, nuclear hormone receptors, enzymes, transporters and other protein targets. We hope that the Concise Guide will provide for researchers, teachers and students a state‐of‐the art source of accurate, curated information on the background to their work that they will use in the Introductions to their Research Papers or Reviews, or in supporting their teaching and studies. We recommend that any citations to information in the Concise Guide are presented in the following format: Alexander SPH et al. (2019). The Concise Guide to PHARMACOLOGY 2019/20: Introduction and Other Protein Targets. Br J Pharmacol 176: S1–S20. In this overview are listed protein targets of pharmacological interest, which are not G protein‐coupled receptors, ion channels, nuclear hormone receptors, catalytic receptors, transporters or enzymes.In order to allow clarity and consistency in pharmacology, there is a need for a comprehensive organisation and presentation of the targets of drugs. This is the philosophy of the IUPHAR/BPS Guide to PHARMACOLOGY presented on the online free access database  also supported the initiation and expansion of the database. We are also tremendously grateful to the long list of collaborators from NC‐IUPHAR subcommittees and beyond, who have assisted in the construction of the Concise Guide to PHARMACOLOGY 2019/20 and the online database http://www.guidetopharmacology.org.We are extremely grateful to the British Pharmacological Society and the International Union of Basic and Clinical Pharmacology, for financial support of the website and for advice from the NC‐IUPHAR subcommittees. We thank the University of Edinburgh, who host the The authors state that there are no conflicts of interest to disclose.http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=1021– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=982– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=970– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=983– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=971– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=910– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=866– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=966– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=997– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=998– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=986– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=901– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=916– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=930– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=915– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=946– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=935– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=784– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=954– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=949– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=985– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=987– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=984– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=868– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=889– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=876– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=888– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=934– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=924– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=919– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=921– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=991– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=941– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=942– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=945– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=929– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=1001– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=906– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=907– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=932– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=905– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=875– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=1000– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=989– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=972– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=1019– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=973– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=974– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=990– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=995– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=996– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=904– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=903– provisional nomenclature, http://www.ensembl.org/Homo_sapiens/Gene/Family/Genes?family=ENSFM00500000270960) respond to the 30 kDa complement‐related protein hormone adiponectin  originally cloned from adipocytes [http://www.ncbi.nlm.nih.gov/pubmed/8619847?dopt=AbstractPlus]. Although sequence data suggest 7TM domains, immunological evidence indicates that, contrary to typical 7TM topology, the carboxyl terminus is extracellular, while the amino terminus is intracellular [http://www.ncbi.nlm.nih.gov/pubmed/12802337?dopt=AbstractPlus]. Signalling through these receptors appears to avoid G proteins; modelling based on the crystal structures of the adiponectin receptors suggested ceramidase acivity, which would make these the first in a new family of catalytic receptors [http://www.ncbi.nlm.nih.gov/pubmed/25855295?dopt=AbstractPlus].Adiponectin receptors  has also been suggested to be a receptor for (hexameric) adiponectin [http://www.ncbi.nlm.nih.gov/pubmed/15210937?dopt=AbstractPlus].T‐Cadherin  Adiponectin: a manifold therapeutic target for metabolic syndrome, diabetes, and coronary disease? Cardiovasc Diabetol13: 103 [https://www.ncbi.nlm.nih.gov/pubmed/24957699?dopt=AbstractPlus]Fisman EZ et al. (2018) Structure and function analysis of adiponectin receptors toward development of novel antidiabetic agents promoting healthy longevity. Endocr J65: 971‐977 [https://www.ncbi.nlm.nih.gov/pubmed/30282888]Okada‐Iwabu M et al. (2016) Adiponectin signaling and function in insulin target tissues. J Mol Cell Biol8: 101‐9 [https://www.ncbi.nlm.nih.gov/pubmed/26993044?dopt=AbstractPlus]Ruan H et al. (2017) Cardiovascular Adiponectin Resistance: The Critical Role of Adiponectin Receptor Modification. Trends Endocrinol. Metab.28: 519‐530 [https://www.ncbi.nlm.nih.gov/pubmed/28473178?dopt=AbstractPlus]Wang Y et al. (2014) Adiponectin and insulin cross talk: the microvascular connection. Trends Cardiovasc. Med.24: 319‐24 [https://www.ncbi.nlm.nih.gov/pubmed/25220977?dopt=AbstractPlus]Zhao L http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=760), degranulation and aggregation of platelets, as well as proteins circulating in the plasma. The coagulation cascade involves multiple proteins being converted to more active forms from less active precursors, typically through proteolysis (see http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=759&familyType=ENZYME). Listed here are the components of the coagulation cascade targetted by agents in current clinical usage.Coagulation as a process is interpreted as a mechanism for reducing excessive blood loss through the generation of a gel‐like clot local to the site of injury. The process involves the activation, adhesion (see Blood125: 2045‐51 [https://www.ncbi.nlm.nih.gov/pubmed/25712994?dopt=AbstractPlus]Astermark J. (2015) FVIII inhibitors: pathogenesis and avoidance. et al. (2017) New clotting disorders that cast new light on blood coagulation and may play a role in clinical practice. J. Thromb. Thrombolysis44: 71‐75 [https://www.ncbi.nlm.nih.gov/pubmed/28251495?dopt=AbstractPlus]Girolami A et al. (2016) Blood flow and mass transfer regulation of coagulation. Blood Rev.30: 357‐68 [https://www.ncbi.nlm.nih.gov/pubmed/27133256?dopt=AbstractPlus]Rana K Bromodomains bind proteins with acetylated lysine residues, such as histones, to regulate gene transcription. Listed herein are examples of bromodomain‐containing proteins for which sufficient pharmacology exists.et al. (2017) Functions of bromodomain‐containing proteins and their roles in homeostasis and cancer. Nat. Rev. Mol. Cell Biol.18: 246‐262 [https://www.ncbi.nlm.nih.gov/pubmed/28053347?dopt=AbstractPlus]Fujisawa T Biochem Pharmacol159: 40‐51 [https://www.ncbi.nlm.nih.gov/pubmed/30414936]Myrianthopoulos V & Mikros E. (2019) From bench to bedside, via desktop. Recent advances in the application of cutting‐edge in silico tools in the research of drugs targeting bromodomain modules. et al. (2017) BET bromodomain proteins and epigenetic regulation of inflammation: implications for type 2 diabetes and breast cancer. Cell. Mol. Life Sci.74: 231‐243 [https://www.ncbi.nlm.nih.gov/pubmed/27491296?dopt=AbstractPlus]Nicholas DA Drug Discov Today23: 76‐89 [https://www.ncbi.nlm.nih.gov/pubmed/28943305]Ramadoss M & Mahadevan V. (2018) Targeting the cancer epigenome: synergistic therapy with bromodomain inhibitors. et al. (2019) Small‐molecule PROTAC degraders of the Bromodomain and Extra Terminal (BET) proteins ‐ A review. Drug Discov Today Technol31: 43‐51 [https://www.ncbi.nlm.nih.gov/pubmed/31200858]Yang CY http://www.ncbi.nlm.nih.gov/pubmed/23716704?dopt=AbstractPlus]. These amyloidogenic mutants are linked to the development of pathological amyloidoses, including familial amyloid polyneuropathy (FAP) , familial amyloid cardiomyopathy (FAC) [http://www.ncbi.nlm.nih.gov/pubmed/9017939?dopt=AbstractPlus], amyloidotic vitreous opacities, carpal tunnel syndrome [http://www.ncbi.nlm.nih.gov/pubmed/10403814?dopt=AbstractPlus] and others. In old age, non‐mutated TTR can also form pathological amyloid fibrils [http://www.ncbi.nlm.nih.gov/pubmed/7016817?dopt=AbstractPlus]. Pharmacological intervention to reduce or prevent TTR dissociation is being pursued as a theapeutic strategy. To date one small molecule kinetic stabilising molecule (http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8378) has been approved for FAP, and is being evaluated in clinical trials for other TTR amyloidoses.Transthyretin (TTR) is a homo‐tetrameric protein which transports thyroxine in the plasma and cerebrospinal fluid and retinol (vitamin A) in the plasma. Many disease causing mutations in the protein have been reported, many of which cause complex dissociation and protein mis‐assembly and deposition of toxic aggregates amyloid fibril formation [et al. (2019) Hereditary transthyretin amyloidosis: a model of medical progress for a fatal disease. Nat Rev Neurol15: 387‐404 [https://www.ncbi.nlm.nih.gov/pubmed/31209302]Adams D et al. (2017) Is transthyretin a good marker of nutritional status? Clin Nutr36: 364‐370 [https://www.ncbi.nlm.nih.gov/pubmed/27381508?dopt=AbstractPlus]Dellière S et al. (2017) Transthyretin amyloidosis: an under‐recognized neuropathy and cardiomyopathy. Clin. Sci.131: 395‐409 [https://www.ncbi.nlm.nih.gov/pubmed/28213611?dopt=AbstractPlus]Galant NJ Biol Pharm Bull41: 979‐984 [https://www.ncbi.nlm.nih.gov/pubmed/29962408]Yokoyama T & Mizuguchi M. (2018) Inhibition of the Amyloidogenesis of Transthyretin by Natural Products and Synthetic Compounds. et al. (2019) Transthyretin Amyloid Cardiomyopathy: JACC State‐of‐the‐Art Review. J Am Coll Cardiol73: 2872‐2891 [https://www.ncbi.nlm.nih.gov/pubmed/31171094]Ruberg FL http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1232) or receptors . Many CDs are targeted for therapeutic gain using antibodies for the treatment of proliferative disorders. A full listing of all the Clusters of Differentiation proteins is not possible in the Guide to PHARMACOLOGY; listed herein are selected members of the family targeted for therapeutic gain.Cluster of differentiation refers to an attempt to catalogue systematically a series of over 300 cell‐surface proteins associated with immunotyping. Many members of the group have identified functions as enzymes ) and programmed cell death 1 ligand 2 . These ligands are cell surface peptides, normally involved in immune system regulation. Expression of PD‐1 by cancer cells induces immune tolerance and evasion of immune system attack. Anti‐PD‐1 monoclonal antibodies are used to induce immune checkpoint blockade as a therapeutic intervention in cancer, effectively re‐establishing immune vigilance. http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7499 was the first anti‐PD‐1 antibody to be approved by the US FDA.The endogenous ligands for human PD‐1 are programmed cell death 1 ligand 1  The glycobiology of the CD system: a dictionary for translating marker designations into glycan/lectin structure and function. Trends Biochem. Sci.40: 360‐76 [https://www.ncbi.nlm.nih.gov/pubmed/25981696?dopt=AbstractPlus]Gabius HJ et al. (2019) CD markers variations in chronic lymphocytic leukemia: New insights into prognosis. J Cell Physiol. 234: 19420‐39 [https://www.ncbi.nlm.nih.gov/pubmed/31049958]Vosoughi T Methyllysine reader proteins bind to methylated proteins, such as histones, allowing regulation of gene expression.et al. (2018) Histone methylation and acetylation in macrophages as a mechanism for regulation of inflammatory responses. J Cell Physiol. 233: 6495‐9507 [https://www.ncbi.nlm.nih.gov/pubmed/29574768]Daskalaki MG et al. (2019) Epigenetic interplays between DNA demethylation and histone methylation for protecting oncogenesis. J Biochem. 165: 297‐299 [https://www.ncbi.nlm.nih.gov/pubmed/30605533]Furuya K Cell Mol Life Sci76: 2873‐83 [https://www.ncbi.nlm.nih.gov/pubmed/31123776]Levy D. (2019) Lysine methylation signaling of non‐histone proteins in the nucleus. et al. (2019) Understanding histone H3 lysine 36 methylation and its deregulation in disease. Cell Mol Life Sci in press [https://www.ncbi.nlm.nih.gov/pubmed/31147750]Li J et al. (2019) Role of histone modification and DNA methylation in signaling pathways involved in diabetic retinopathy. J Cell Physiol.234: 7839‐7846 [https://www.ncbi.nlm.nih.gov/pubmed/30515789]Shafabakhsh R e.g. in plasma) or transport these agents; to the nucleus to interact with nuclear receptors  or for interaction with metabolic enzymes. Although sequence homology is limited, crystallographic studies suggest conserved 3D structures across the group of binding proteins.Fatty acid‐binding proteins are low molecular weight (100‐130 aa) chaperones for long chain fatty acids, fatty acyl CoA esters, eicosanoids, retinols, retinoic acids and related metabolites and are usually regarded as being responsible for allowing the otherwise hydrophobic ligands to be mobile in aqueous media. These binding proteins may perform functions extracellularly (http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6735 exhibits high affinity for FABP4 (pIC50 8.8) compared to FABP3 or FABP5 (pIC50 <6.6) . http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6736 is reported to interfere with FABP4 action [http://www.ncbi.nlm.nih.gov/pubmed/19754198?dopt=AbstractPlus]. Ibuprofen displays some selectivity for FABP4 (pIC50 5.5) relative to FABP3 (pIC50 3.5) and FABP5 (pIC50 3.8) [http://www.ncbi.nlm.nih.gov/pubmed/24248795?dopt=AbstractPlus]. Fenofibric acid displays some selectivity for FABP5 (pIC50 5.5) relative to FABP3 (pIC50 4.5) and FABP4 (pIC50 4.6) [http://www.ncbi.nlm.nih.gov/pubmed/24248795?dopt=AbstractPlus]. Multiple pseudogenes for the FABPs have been identified in the human genome.Although not tested at all FABPs, et al. (2015) Enterocyte fatty acid‐binding proteins (FABPs): different functions of liver and intestinal FABPs in the intestine. Prostaglandins Leukot. Essent. Fatty Acids93: 9‐16 [https://www.ncbi.nlm.nih.gov/pubmed/25458898?dopt=AbstractPlus]Gajda AM Prostaglandins Leukot Essent Fatty Acids93: 45‐9 [https://www.ncbi.nlm.nih.gov/pubmed/25154384?dopt=AbstractPlus]Glatz JF. (2015) Lipids and lipid binding proteins: a perfect match. et al. (2015) Metabolic functions of FABPs–mechanisms and therapeutic implications. Nat Rev Endocrinol11: 592‐605 [https://www.ncbi.nlm.nih.gov/pubmed/26260145?dopt=AbstractPlus]Hotamisligil GS et al. (2016) Fatty acid binding proteins and the nervous system: Their impact on mental conditions. Neurosci. Res.102: 47‐55 [https://www.ncbi.nlm.nih.gov/pubmed/25205626?dopt=AbstractPlus]Matsumata M et al. (2016) Heart lipid droplets and lipid droplet‐binding proteins: Biochemistry, physiology, and pathology. Exp. Cell Res.340: 198‐204 [https://www.ncbi.nlm.nih.gov/pubmed/26524506?dopt=AbstractPlus]Osumi T http://www.ncbi.nlm.nih.gov/pubmed/20971825?dopt=AbstractPlus]. As the Notch ligands are also membrane bound, cells have to be in close proximity for receptorligand interactions to occur. Cleavage of the intracellular domain (ICD) of activated Notch receptors by γ‐secretase is required for downstream signalling and Notch‐induced transcriptional modulation . This is why γ‐secretase inhibitors can be used to downregulate Notch signalling and explains their anticancer action. One such small molecule is http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7338 [http://www.ncbi.nlm.nih.gov/pubmed/19773430?dopt=AbstractPlus], although development of this compound has been terminated following an unsuccessful Phase II single agent clinical trial in metastatic colorectal cancer [http://www.ncbi.nlm.nih.gov/pubmed/22445247?dopt=AbstractPlus].The canonical Notch signalling pathway has four type I transmembrane Notch receptors (Notch1‐4) and five ligands . Each member of this highly conserved receptor family plays a unique role in cell‐fate determination during embryogenesis, differentiation, tissue patterning, proliferation and cell death , with http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8451 and http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8453 identified as antibody inhibitors of ligand:receptor binding [http://www.ncbi.nlm.nih.gov/pubmed/25388163?dopt=AbstractPlus].Aberrant Notch signalling is implicated in a number of human cancers [et al. (2018) Notch signaling and neuronal death in stroke. Prog. Neurobiol.165‐167: 103‐116 [https://www.ncbi.nlm.nih.gov/pubmed/29574014?dopt=AbstractPlus]Arumugam TV et al. (2016) The Notch intracellular domain integrates signals from Wnt, Hedgehog, TGFβ/BMP and hypoxia pathways. Biochim. Biophys. Acta1863: 303‐13 [https://www.ncbi.nlm.nih.gov/pubmed/26592459?dopt=AbstractPlus]Borggrefe T et al. (2015) Ligand‐Independent Mechanisms of Notch Activity. Trends Cell Biol.25: 697‐707 [https://www.ncbi.nlm.nih.gov/pubmed/26437585?dopt=AbstractPlus]Palmer WH et al. (2015) Molecular pathways: translational and therapeutic implications of the Notch signaling pathway in cancer. Clin. Cancer Res.21: 955‐61 [https://www.ncbi.nlm.nih.gov/pubmed/25388163?dopt=AbstractPlus]Previs RA et al. (2015) Targeting Notch, Hedgehog, and Wnt pathways in cancer stem cells: clinical update. Nat Rev Clin Oncol12: 445‐64 [https://www.ncbi.nlm.nih.gov/pubmed/25850553?dopt=AbstractPlus]Takebe N http://www.ncbi.nlm.nih.gov/pubmed/8756726?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/9108480?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/9417641?dopt=AbstractPlus], leading to a termination of GPCR signalling. Interactions through protein: protein interactions of many RGS proteins have been identified for targets other than heteromeric G proteins. Sequence analysis of the 20 RGS proteins suggests four families of RGS: RZ, R4, R7 and R12 families. Many of these proteins have been identified to have effects other than through targetting G proteins. Included here is RGS4 for which a number of pharmacological inhibitors have been described.Regulators of G protein signalling (RGS) proteins display a common RGS domain that interacts with the GTP‐bound Gα subunits of heterotrimeric G proteins, enhancing GTP hydrolysis by stabilising the transition state [http://www.ncbi.nlm.nih.gov/pubmed/16765607?dopt=AbstractPlus]. It consists of RGS17 , RGS19  and RGS20 . All members contain an N‐terminal cysteine string motif [http://www.ncbi.nlm.nih.gov/pubmed/17183362?dopt=AbstractPlus] which is a site of palmitoylation and could serve functions in membrane targeting, protein stability or aid protein‐protein interactions [http://www.ncbi.nlm.nih.gov/pubmed/17126529?dopt=AbstractPlus]. However, the function in the case of RZ family RGS proteins is not yet fully understood. Members of the RZ family of RGS proteins are the only RGS proteins that have selective GTPase activating‐protein (GAP) activity for Gαz, a function that resulted in the name of the family . However, the members of the RZ family are able to also GAP Gαi/o members with varying selectivity.The RZ family of RGS proteins is less well characterized than the other families [This is the largest family of RGS proteins.This family of RGS proteins shows some selectivity for Gai/o proteins.http://www.ncbi.nlm.nih.gov/pubmed/26123306?dopt=AbstractPlus]. The Gαi/o‐Loco (GoLoco) motif in RGS12 and 14 has GDI activity (for Guanine nucleotide Dissociation Inhibitor) towards Gαi1, Gαi2 and Gαi3 . Through this activity RGS12 and RGS14 can inhibit G protein signaling both by accelerating GTP hydrolysis and by preventing G protein activation. Splice variants of RGS12 and RGS14 also contain membrane targeting and protein‐protein interaction domains .The R12 family consists of RGS10, 12 and 14. RGS12 and 14 are large proteins with additional domains that can participate in protein‐protein interactions and other functions. In contrast, RGS10 is a small protein consisting of the RGS domain and small N‐ and C‐termini, similar to members of the R4 family. However, sequence homology of the RGS10 RGS domain clearly places it in the R12 family Alqinyah M et al. (2002) Regulators of G‐protein signalling as new central nervous system drug targets. Nat Rev Drug Discov1: 187‐97 [https://www.ncbi.nlm.nih.gov/pubmed/12120503?dopt=AbstractPlus]Neubig RR et al. (2010) Non‐canonical functions of RGS proteins. Cell. Signal.22: 1274‐81 [https://www.ncbi.nlm.nih.gov/pubmed/20363320?dopt=AbstractPlus]Sethakorn N Br. J. Pharmacol.174: 427‐437 [https://www.ncbi.nlm.nih.gov/pubmed/28098342?dopt=AbstractPlus]Sjögren B. (2017) The evolution of regulators of G protein signalling proteins as drug targets ‐ 20 years in the making: IUPHAR Review 21. et al. (2010) Thinking outside of the ‘RGS box’: new approaches to therapeutic targeting of regulators of G protein signaling. Mol. Pharmacol.78: 550‐7 [https://www.ncbi.nlm.nih.gov/pubmed/20664002?dopt=AbstractPlus]Sjögren B http://www.ncbi.nlm.nih.gov/pubmed/27042935?dopt=AbstractPlus] suggests a trimeric structure of a single short transmembrane domain traversing the endoplasmic reticulum membrane, with the bulk of the protein facing the cytosol. A wide range of compounds, ranging from psychoactive agents to antihistamines, have been observed to bind to these sites.Although termed ’receptors’, the evidence for coupling through conventional signalling pathways is lacking. Initially described as a subtype of opioid receptors, there is only a modest pharmacological overlap and no structural convergence with the G protein‐coupled receptors; the crystal structure of the sigma1 receptor [http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1606 also shows activity at opioid receptors. The sigma2 receptor has recently been reported to be http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2553 [http://www.ncbi.nlm.nih.gov/pubmed/28559337?dopt=AbstractPlus], a 4TM protein partner of NPC1, the Niemann‐Pick C1 protein, a 13TM cholesterol‐binding protein.et al. (2016) Biochemical Pharmacology of the Sigma‐1 Receptor. Mol. Pharmacol.89: 142‐53 [https://www.ncbi.nlm.nih.gov/pubmed/26560551?dopt=AbstractPlus]Chu UB et al. (2015) Sigma‐1 receptor and inflammatory pain. Inflamm. Res.64: 377‐81 [https://www.ncbi.nlm.nih.gov/pubmed/25902777?dopt=AbstractPlus]Gris G et al. (2016) Sigma receptors [σRs]: biology in normal and diseased states. J. Recept. Signal Transduct. Res.36: 327‐388 [https://www.ncbi.nlm.nih.gov/pubmed/26056947?dopt=AbstractPlus]Rousseaux CG et al. (2018) The sigma‐1 receptor as a regulator of dopamine neurotransmission: A potential therapeutic target for methamphetamine addiction. Pharmacol Ther186: 152‐167 [https://www.ncbi.nlm.nih.gov/pubmed/29360540]Sambo DO et al. (2016) The Sigma‐1 Receptor as a Pluripotent Modulator in Living Systems. Trends Pharmacol. Sci.37: 262‐278 [https://www.ncbi.nlm.nih.gov/pubmed/26869505?dopt=AbstractPlus]Su TP et al. (2019) Allosteric Modulators of Sigma‐1 Receptor: A Review. Front Pharmacol10: 223 [https://www.ncbi.nlm.nih.gov/pubmed/30941035]Vavers E Tubulins are a family of intracellular proteins most commonly associated with microtubules, part of the cytoskeleton. They are exploited for therapeutic gain in cancer chemotherapy as targets for agents derived from a variety of natural products: taxanes, colchicine and vinca alkaloids. These are thought to act primarily through β‐tubulin, thereby interfering with the normal processes of tubulin polymer formation and disassembly.et al. (2019) Current advances of tubulin inhibitors as dual acting small molecules for cancer therapy. Med Res Rev39: 1398‐1426 [https://www.ncbi.nlm.nih.gov/pubmed/30746734]Arnst KE Proc Natl Acad Sci U S A116: 10366‐10371 [https://www.ncbi.nlm.nih.gov/pubmed/31072936]Eshun‐Wilson L. (2019) Effects of alpha‐tubulin acetylation on microtubule structure and stability. et al. (2017) The tubulin code at a glance. J. Cell. Sci.130: 1347‐1353 [https://www.ncbi.nlm.nih.gov/pubmed/28325758?dopt=AbstractPlus]Gadadhar S et al. (2018) Tubulin Posttranslational Modifications and Emerging Links to Human Disease. Cell173: 1323‐1327 [https://www.ncbi.nlm.nih.gov/pubmed/29856952]Magiera MM et al. (2017) Anti‐mitotic agents: Are they emerging molecules for cancer treatment? Pharmacol. Ther.173: 67‐82 [https://www.ncbi.nlm.nih.gov/pubmed/28174095?dopt=AbstractPlus]Penna LS


This article has been corrected: The correct author information is given below:Pin Li2,1,*and Xu Zhang1,2https://doi.org/10.18632/oncotarget.19934Original article: Oncotarget. 2017; 8:62489-62499.