Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT0PZR5)

• DTT Name: Leukotriene CysLT2 receptor (CYSLTR2)
• 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
• Gene Name: CYSLTR2
• DTT Type: Clinical trial target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: CLTR2_HUMAN
• TTD ID: T74238
• Sequence:
  MERKFMSLQPSISVSEMEPNGTFSNNNSRNCTIENFKREFFPIVYLIIFFWGVLGNGLSI
  YVFLQPYKKSTSVNVFMLNLAISDLLFISTLPFRADYYLRGSNWIFGDLACRIMSYSLYV
  NMYSSIYFLTVLSVVRFLAMVHPFRLLHVTSIRSAWILCGIIWILIMASSIMLLDSGSEQ
  NGSVTSCLELNLYKIAKLQTMNYIALVVGCLLPFFTLSICYLLIIRVLLKVEVPESGLRV
  SHRKALTTIIITLIIFFLCFLPYHTLRTVHLTTWKVGLCKDRLHKALVITLALAAANACF
  NPLLYYFAGENFKDRLKSALRKGHPQKAKTKCVFPVSVWLRKETRV
• 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.
• KEGG Pathway:
  Calcium signaling pathway (hsa04020)
  Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  Leukotriene receptors (R-HSA-391906)

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BAY-X-7195	DM2XE80	Asthma	CA23	Phase 2	[1]

7 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AS-35	DMC2WI7	Asthma	CA23	Discontinued in Phase 2	[2]
DS-4574	DM8GZWC	Asthma	CA23	Discontinued in Phase 2	[3]
Sulukast	DMBSLZV	Asthma	CA23	Discontinued in Phase 2	[4]
FPL-55712	DMF1CDK	Asthma	CA23	Terminated	[5]
ICI-198615	DM0195G	Asthma	CA23	Terminated	[6]
LY-290154	DMPZ7AO	Asthma	CA23	Terminated	[7]
MDL-43291	DMBIDQX	Asthma	CA23	Terminated	[8]

10 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BayCysLT2	DMKFTZA	Discovery agent	N.A.	Investigative	[9]
BAYu9773	DMXQ14V	Discovery agent	N.A.	Investigative	[10]
CGP-57698	DMYZ72J	Discovery agent	N.A.	Investigative	[11]
HAMI3379	DMJN0BL	Discovery agent	N.A.	Investigative	[12]
LTC4	DM702WR	Discovery agent	N.A.	Investigative	[13]
LTD4	DMIUZX3	Discovery agent	N.A.	Investigative	[13]
LTE4	DMCPB0Q	Discovery agent	N.A.	Investigative	[14]
N-methyl LTC4	DM6XYCU	Discovery agent	N.A.	Investigative	[14]
pobilukast	DMURB4Y	Discovery agent	N.A.	Investigative	[15]
[3H]LTC4	DMD09BO	Discovery agent	N.A.	Investigative	[16]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Asthma	CA23	Nasal and bronchial airway	1.40E-03	-0.24	-0.52

References

• [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.
• [2] Inhibition of radiolabeled leukotriene-binding by AS-35 in guinea pig lung membrane fraction. Jpn J Pharmacol. 1992 Apr;58(4):357-64.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] Heterogeneity of binding sites for ICI 198,615 in human lung parenchyma. Biochem Pharmacol. 1992 Oct 6;44(7):1411-5.
• [7] DOI: 10.1021/op060036x
• [8] 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.
• [9] 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.
• [10] BAY u9773, a novel antagonist of cysteinyl-leukotrienes with activity against two receptor subtypes. Eur J Pharmacol. 1994 Nov 3;264(3):317-23.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] 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).
• [16] 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.