Target Information

Target General Infomation
Target ID
T71192
Former ID
TTDS00183
Target Name
Cysteinyl leukotriene receptor 1
Gene Name
CYSLTR1
Synonyms
CysLTR1; Cysteinyl leukotriene D4 receptor; HG55; HMTMF81; LTD4 receptor; Leukotriene D4-receptor; CYSLTR1
Target Type
Successful
Disease Asthma [ICD10: J45]
Asthma; Prophylaxis [ICD9: 493; ICD10: J45]
Allergy [ICD9: 995.3; ICD10: T78.4]
Allergic rhinitis [ICD9: 472.0, 477, 995.3; ICD10: J00, J30, J31.0, T78.4]
Migraine [ICD9: 346; ICD10: G43]
Unspecified [ICD code not available]
Function
Receptor for cysteinyl leukotrienes mediating bronchoconstriction of individuals with and without asthma. Stimulation by LTD4 results in the contraction and proliferation of smooth muscle, edema, eosinophil migration and damage to the mucus layer in the lung. This response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system. The rank order of affinities for the leukotrienes is LTD4 >>LTE4 = LTC4 >> LTB4.
BioChemical Class
GPCR rhodopsin
Target Validation
T71192
UniProt ID
Q9Y271
Sequence
MDETGNLTVSSATCHDTIDDFRNQVYSTLYSMISVVGFFGNGFVLYVLIKTYHKKSAFQV
YMINLAVADLLCVCTLPLRVVYYVHKGIWLFGDFLCRLSTYALYVNLYCSIFFMTAMSFF
RCIAIVFPVQNINLVTQKKARFVCVGIWIFVILTSSPFLMAKPQKDEKNNTKCFEPPQDN
QTKNHVLVLHYVSLFVGFIIPFVIIIVCYTMIILTLLKKSMKKNLSSHKKAIGMIMVVTA
AFLVSFMPYHIQRTIHLHFLHNETKPCDSVLRMQKSVVITLSLAASNCCFDPLLYFFSGG
NFRKRLSTFRKHSLSSVTYVPRKKASLPEKGEEICKV
Drugs and Mode of Action
Drug(s) Cinalukast Drug Info Approved Asthma [1]
Montelukast Drug Info Approved Asthma [2], [3]
Pranlukast Drug Info Approved Asthma; Prophylaxis [2], [4]
Zafirlukast Drug Info Approved Asthma [5], [6]
Claritin/Singulair Drug Info Phase 3 Allergic rhinitis [7], [8], [9]
BAY-X-7195 Drug Info Phase 2 Asthma [10]
Iralukast Drug Info Phase 2 Asthma [11], [12]
KP-496 Drug Info Phase 2 Asthma [13]
LM-1507.NA Drug Info Phase 2 Asthma [14]
Masilukast Drug Info Phase 2 Asthma [15]
CR-3465 Drug Info Phase 1 Allergy [16]
YM-57158 Drug Info Phase 1 Allergic rhinitis [17]
Ablukast Drug Info Discontinued in Phase 3 Asthma [18]
AS-35 Drug Info Discontinued in Phase 2 Asthma [19]
DS-4574 Drug Info Discontinued in Phase 2 Asthma [20]
FK-011 Drug Info Discontinued in Phase 2 Asthma [21]
L-660771 Drug Info Discontinued in Phase 2 Discovery agent [22], [23]
LY-2300559 Drug Info Discontinued in Phase 2 Migraine [24]
Sulukast Drug Info Discontinued in Phase 2 Asthma [25], [26]
RG-7152 Drug Info Discontinued in Phase 1 Asthma [27]
FPL-55712 Drug Info Terminated Asthma [28]
L-648051 Drug Info Terminated Asthma [29]
LM-1376 Drug Info Terminated Asthma [30]
LY-290154 Drug Info Terminated Asthma [31]
MCI-826 Drug Info Terminated Asthma [32]
MDL-43291 Drug Info Terminated Asthma [33]
OT-4003 Drug Info Terminated Asthma [34]
Tomelukast Drug Info Terminated Asthma [35]
Antagonist 5'-methylthioadenosine Drug Info [36]
BayCysLT2 Drug Info [37]
BAYu9773 Drug Info [38]
Cinalukast Drug Info [1]
LM-1507.NA Drug Info [39], [9]
MCI-826 Drug Info [40], [9]
Montelukast Drug Info [41], [42]
pobilukast Drug Info [43]
Pranlukast Drug Info [44]
RG-7152 Drug Info [27], [9]
XGP-510 Drug Info [45]
Zafirlukast Drug Info [5], [41], [46]
[3H]ICI-198615 Drug Info [47]
Modulator Ablukast Drug Info [48]
AS-35 Drug Info [49]
BAY-X-7195 Drug Info
CGP-57698 Drug Info
Claritin/Singulair Drug Info [7], [8]
CR-3465 Drug Info [48]
DS-4574 Drug Info [50]
FK-011 Drug Info [51]
FPL-55712 Drug Info [52]
Iralukast Drug Info [53]
KP-496 Drug Info [13]
L-648051 Drug Info
L-660771 Drug Info
LM-1376 Drug Info [54]
LY-2300559 Drug Info
LY-290154 Drug Info
Masilukast Drug Info [48]
MDL-43291 Drug Info
OT-4003 Drug Info [34]
Sulukast Drug Info
Tomelukast Drug Info
WY-46016 Drug Info
YM-57158 Drug Info [17]
Agonist LTC4 Drug Info [55]
LTD4 Drug Info [43]
LTE4 Drug Info [55]
N-methyl LTC4 Drug Info [56]
[3H]LTD4 Drug Info [45]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Calcium signaling pathway
Neuroactive ligand-receptor interaction
NetPath Pathway TGF_beta_Receptor Signaling Pathway
IL4 Signaling Pathway
IL3 Signaling Pathway
Pathway Interaction Database Endothelins
Reactome Leukotriene receptors
G alpha (q) signalling events
WikiPathways GPCRs, Class A Rhodopsin-like
Gastrin-CREB signalling pathway via PKC and MAPK
GPCR ligand binding
GPCR downstream signaling
References
REF 1Prolonged protection against exercise-induced bronchoconstriction by the leukotriene D4-receptor antagonist cinalukast. J Allergy Clin Immunol. 1997 Feb;99(2):210-5.
REF 2Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. Epub 2007 Feb 20.
REF 3(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: 3340).
REF 4(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: 3634).
REF 5Role of antileukotriene agents in asthma therapy. J Am Osteopath Assoc. 2000 Jan;100(1):32, 37-43.
REF 6(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: 3322).
REF 7Montelukast, a leukotriene receptor antagonist, for the treatment of persistent asthma in children aged 2 to 5 years. Pediatrics. 2001 Sep;108(3):E48.
REF 8A review of montelukast in the treatment of asthma and allergic rhinitis. Expert Opin Pharmacother. 2004 Mar;5(3):679-86.
REF 9Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
REF 10Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003794)
REF 11Iralukast Novartis AG. IDrugs. 1998 May;1(1):147-50.
REF 12(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: 5861).
REF 13Effects of KP-496, a novel dual antagonist for leukotriene D4 and thromboxane A2 receptors, on contractions induced by various agonists in the guinea pig trachea. Allergol Int. 2006 Dec;55(4):403-10.
REF 14Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010469)
REF 15Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800015230)
REF 16Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800019601)
REF 17In vitro pharmacologic profile of YM158, a new dual antagonist for LTD4 and TXA2 receptors. J Pharmacol Exp Ther. 1998 Nov;287(2):633-9.
REF 18Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002358)
REF 19Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001439)
REF 20Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000587)
REF 21Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010718)
REF 22(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: 6193).
REF 23Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000074)
REF 24ClinicalTrials.gov (NCT01184508) A Study in Migraine Prevention. U.S. National Institutes of Health.
REF 25(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 26Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000090)
REF 27Induction of peroxisomal enzymes by a tetrazole-substituted 2-quinolinylmethoxy leukotriene D4 antagonist. Fundam Appl Toxicol. 1994 Aug;23(2):298-303.
REF 28Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000089)
REF 29Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000103)
REF 30Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006199)
REF 31Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007201)
REF 32Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001711)
REF 33Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000087)
REF 34Discovery of OT4003, a novel, potent, and orally active cys-LT1 receptor antagonist. Bioorg Med Chem. 1997 Feb;5(2):415-27.
REF 35Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000075)
REF 36Inhibition of the tyrosine kinase activity of the fibroblast growth factor receptor by the methyltransferase inhibitor 5'-methylthioadenosine. J Biol Chem. 1993 Feb 25;268(6):4244-9.
REF 37Synthesis 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 38Molecular 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 39Pharmacological differences among CysLT(1) receptor antagonists with respect to LTC(4) and LTD(4) in human lung parenchyma. Biochem Pharmacol. 2002 Apr 15;63(8):1537-46.
REF 40Leukotriene receptors in the skin of rats differ from those of mouse skin or rat stomach strip. Eur J Pharmacol. 1992 Oct 20;221(2-3):333-42.
REF 41Knockouts model the 100 best-selling drugs--will they model the next 100? Nat Rev Drug Discov. 2003 Jan;2(1):38-51.
REF 42Protective Potential of Montelukast Against Hepatic Ischemia/Reperfusion Injury in Rats. J Surg Res. 2008 Sep 7.
REF 43Identification, molecular cloning, expression, and characterization of a cysteinyl leukotriene receptor. Mol Pharmacol. 1999 Sep;56(3):657-63.
REF 44Beneficial effects of leukotriene receptor antagonists in the prevention of cedar pollinosis in a community setting. J Investig Allergol Clin Immunol. 2009;19(3):195-203.
REF 45(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: 269).
REF 46Inhibitory effects of zafirlukast on respiratory bursts of human neutrophils. Drugs Exp Clin Res. 2002;28(4):133-45.
REF 47Heterogeneity of binding sites for ICI 198,615 in human lung parenchyma. Biochem Pharmacol. 1992 Oct 6;44(7):1411-5.
REF 48Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
REF 49Peptide leukotriene antagonistic activity of AS-35, a new antiallergic drug. Jpn J Pharmacol. 1992 Apr;58(4):347-55.
REF 50Inhibitory 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 51Evaluation of human peroxisome proliferator-activated receptor (PPAR) subtype selectivity of a variety of anti-inflammatory drugs based on a novel assay for PPAR delta(beta). J Pharmacol Sci. 2003 Nov;93(3):347-55.
REF 52Effect 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 53Pharmacological characterization of the cysteinyl-leukotriene antagonists CGP 45715A (iralukast) and CGP 57698 in human airways in vitro. Br J Pharmacol. 1998 Feb;123(3):590-8.
REF 54Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
REF 55Characterization of the human cysteinyl leukotriene CysLT1 receptor. Nature. 1999 Jun 24;399(6738):789-93.
REF 56Differential 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.

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