Target Information
Target General Information | Top | |||||
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Target ID |
T74238
(Former ID: TTDI01916)
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Target Name |
Leukotriene CysLT2 receptor (CYSLTR2)
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Synonyms |
hGPCR21; PSEC0146; HPN321; Gprotein coupled receptor HG57; Gprotein coupled receptor GPCR21; G-protein coupled receptor HG57; G-protein coupled receptor GPCR21; Cysteinyl leukotriene receptor 2; CysLTR2; CYSLT2R; CYSLT2
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Gene Name |
CYSLTR2
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Asthma [ICD-11: CA23] | |||||
Function |
The response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system. Stimulation by BAY u9773, a partial agonist, induces specific contractions of pulmonary veins and might also have an indirect role in the relaxation of the pulmonary vascular endothelium. The rank order of affinities for the leukotrienes is LTC4 = LTD4 >> LTE4. Receptor for cysteinyl leukotrienes.
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BioChemical Class |
GPCR rhodopsin
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UniProt ID | ||||||
Sequence |
MERKFMSLQPSISVSEMEPNGTFSNNNSRNCTIENFKREFFPIVYLIIFFWGVLGNGLSI
YVFLQPYKKSTSVNVFMLNLAISDLLFISTLPFRADYYLRGSNWIFGDLACRIMSYSLYV NMYSSIYFLTVLSVVRFLAMVHPFRLLHVTSIRSAWILCGIIWILIMASSIMLLDSGSEQ NGSVTSCLELNLYKIAKLQTMNYIALVVGCLLPFFTLSICYLLIIRVLLKVEVPESGLRV SHRKALTTIIITLIIFFLCFLPYHTLRTVHLTTWKVGLCKDRLHKALVITLALAAANACF NPLLYYFAGENFKDRLKSALRKGHPQKAKTKCVFPVSVWLRKETRV Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold |
Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
1 | BAY-X-7195 | Drug Info | Phase 2 | Asthma | [2] | |
Discontinued Drug(s) | [+] 7 Discontinued Drugs | + | ||||
1 | AS-35 | Drug Info | Discontinued in Phase 2 | Asthma | [3] | |
2 | DS-4574 | Drug Info | Discontinued in Phase 2 | Asthma | [4] | |
3 | Sulukast | Drug Info | Discontinued in Phase 2 | Asthma | [5], [6] | |
4 | FPL-55712 | Drug Info | Terminated | Asthma | [7] | |
5 | ICI-198615 | Drug Info | Terminated | Asthma | [8], [9] | |
6 | LY-290154 | Drug Info | Terminated | Asthma | [10] | |
7 | MDL-43291 | Drug Info | Terminated | Asthma | [11] | |
Mode of Action | [+] 3 Modes of Action | + | ||||
Modulator | [+] 8 Modulator drugs | + | ||||
1 | BAY-X-7195 | Drug Info | [1] | |||
2 | AS-35 | Drug Info | [12], [13] | |||
3 | DS-4574 | Drug Info | [14], [15] | |||
4 | Sulukast | Drug Info | [16] | |||
5 | FPL-55712 | Drug Info | [17] | |||
6 | LY-290154 | Drug Info | [19] | |||
7 | MDL-43291 | Drug Info | [20] | |||
8 | CGP-57698 | Drug Info | [23] | |||
Antagonist | [+] 5 Antagonist drugs | + | ||||
1 | ICI-198615 | Drug Info | [18] | |||
2 | BayCysLT2 | Drug Info | [21] | |||
3 | BAYu9773 | Drug Info | [22] | |||
4 | HAMI3379 | Drug Info | [24] | |||
5 | pobilukast | Drug Info | [28] | |||
Agonist | [+] 5 Agonist drugs | + | ||||
1 | LTC4 | Drug Info | [25] | |||
2 | LTD4 | Drug Info | [25], [26] | |||
3 | LTE4 | Drug Info | [27] | |||
4 | N-methyl LTC4 | Drug Info | [27] | |||
5 | [3H]LTC4 | Drug Info | [29] |
Cell-based Target Expression Variations | Top | |||||
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Cell-based Target Expression Variations |
Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Human Similarity Proteins
Human Pathway Affiliation
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KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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Calcium signaling pathway | hsa04020 | Affiliated Target |
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Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
Neuroactive ligand-receptor interaction | hsa04080 | Affiliated Target |
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Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy |
Chemical Structure based Activity Landscape of Target | Top |
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Drug Property Profile of Target | Top | |
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(1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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(5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five |
Target Poor or Non Binders | Top | |||||
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Target Poor or Non Binders |
Target Regulators | Top | |||||
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Target-interacting Proteins |
Target Profiles in Patients | Top | |||||
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Target Expression Profile (TEP) |
Target Affiliated Biological Pathways | Top | |||||
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KEGG Pathway | [+] 2 KEGG Pathways | + | ||||
1 | Calcium signaling pathway | |||||
2 | Neuroactive ligand-receptor interaction | |||||
NetPath Pathway | [+] 2 NetPath Pathways | + | ||||
1 | IL4 Signaling Pathway | |||||
2 | IL3 Signaling Pathway | |||||
PID Pathway | [+] 1 PID Pathways | + | ||||
1 | Endothelins | |||||
Reactome | [+] 2 Reactome Pathways | + | ||||
1 | Leukotriene receptors | |||||
2 | G alpha (q) signalling events | |||||
WikiPathways | [+] 4 WikiPathways | + | ||||
1 | GPCRs, Class A Rhodopsin-like | |||||
2 | Gastrin-CREB signalling pathway via PKC and MAPK | |||||
3 | GPCR ligand binding | |||||
4 | GPCR downstream signaling |
References | Top | |||||
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REF 1 | The effect of a novel leukotriene C4/D4 antagonist, BAY-x-7195, on experimental allergic reactions. Prostaglandins. 1995 Nov-Dec;50(5-6):269-85. | |||||
REF 2 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003794) | |||||
REF 3 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001439) | |||||
REF 4 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000587) | |||||
REF 5 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 3327). | |||||
REF 6 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000090) | |||||
REF 7 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000089) | |||||
REF 8 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 3358). | |||||
REF 9 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002386) | |||||
REF 10 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007201) | |||||
REF 11 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000087) | |||||
REF 12 | Inhibition of radiolabeled leukotriene-binding by AS-35 in guinea pig lung membrane fraction. Jpn J Pharmacol. 1992 Apr;58(4):357-64. | |||||
REF 13 | Peptide leukotriene antagonistic activity of AS-35, a new antiallergic drug. Jpn J Pharmacol. 1992 Apr;58(4):347-55. | |||||
REF 14 | Inhibitory effect of DS-4574, a mast cell stabilizer with peptidoleukotriene receptor antagonism, on gastric acid secretion in rats. Eur J Pharmacol. 1994 Apr 1;255(1-3):229-34. | |||||
REF 15 | Antagonistic action of DS-4574 against leukotrienes in guinea-pig smooth muscle. Arch Int Pharmacodyn Ther. 1991 Nov-Dec;314:147-59. | |||||
REF 16 | The pharmacological evaluation of LY 170680, a novel leukotriene D4 and E4 antagonist in the guinea-pig. Br J Pharmacol. 1989 Sep;98(1):259-67. | |||||
REF 17 | Effect of the leukotriene receptor antagonists FPL 55712, LY 163443, and MK-571 on the elimination of cysteinyl leukotrienes in the rat. Br J Pharmacol. 1991 Apr;102(4):865-70. | |||||
REF 18 | Heterogeneity of binding sites for ICI 198,615 in human lung parenchyma. Biochem Pharmacol. 1992 Oct 6;44(7):1411-5. | |||||
REF 19 | DOI: 10.1021/op060036x | |||||
REF 20 | Conformationally restricted leukotriene receptor antagonists: [(octahydro-2-oxo-7-tetradecylidene-2H-1-benzopyran-8-yl)thio]ace tic acids. Pharmacology. 1990;40(5):271-6. | |||||
REF 21 | Synthesis of cysteinyl leukotrienes in human endothelial cells: subcellular localization and autocrine signaling through the CysLT2 receptor. FASEB J. 2011 Oct;25(10):3519-28. | |||||
REF 22 | BAY u9773, a novel antagonist of cysteinyl-leukotrienes with activity against two receptor subtypes. Eur J Pharmacol. 1994 Nov 3;264(3):317-23. | |||||
REF 23 | A kinetic binding study to evaluate the pharmacological profile of a specific leukotriene C(4) binding site not coupled to contraction in human lun... Mol Pharmacol. 2000 Jun;57(6):1182-9. | |||||
REF 24 | Pharmacological characterization of the first potent and selective antagonist at the cysteinyl leukotriene 2 (CysLT(2)) receptor. Br J Pharmacol. 2010 May;160(2):399-409. | |||||
REF 25 | Molecular cloning and characterization of a second human cysteinyl leukotriene receptor: discovery of a subtype selective agonist. Mol Pharmacol. 2000 Dec;58(6):1601-8. | |||||
REF 26 | Characterization of the human cysteinyl leukotriene 2 receptor. J Biol Chem. 2000 Sep 29;275(39):30531-6. | |||||
REF 27 | Differential signaling of cysteinyl leukotrienes and a novel cysteinyl leukotriene receptor 2 (CysLT agonist, N-methyl-leukotriene C in calcium reporter and beta arrestin assays. Mol Pharmacol. 2011 Feb;79(2):270-8. | |||||
REF 28 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 270). | |||||
REF 29 | The molecular characterization and tissue distribution of the human cysteinyl leukotriene CysLT(2) receptor. Biochem Biophys Res Commun. 2000 Aug 2;274(2):316-22. |
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