Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DM0195G)

• Drug Name: ICI-198615 Drug Info
• Synonyms: Cyclopentyl N-[1-[[4-(benzenesulfonylcarbamoyl)-2-methoxyphenyl]methyl]indazol-6-yl]carbamate; Ici 198615; 104448-53-5; CHEMBL22033; Ici-198,615; ZM 198615; ZM-198,615; cyclopentyl N-[1-({4-[(benzenesulfonyl)carbamoyl]-2-methoxyphenyl}methyl)-1H-indazol-6-yl]carbamate; [3H]ICI198615; [3H]-ICI198615; [3H]ICI-198615; [3H]ICI-198,615; AC1L3GQZ; (1-((2-Methoxy-4-(((phenylsulfonyl)amino)carbonyl)phenyl)methyl)-1H-indazol-6-yl)carbamic acid cyclopentyl ester; GTPL3414; GTPL3358; SCHEMBL9806720; DTXSID80146490; BDBM50009075; PDSP1_000520; PDSP2_000518; ICI198615

Indication

Disease Entry	ICD 11	Status	REF
Asthma	CA23	Terminated	[1]

• Cross-matching ID:
  PubChem CID: 115219
  CAS Number: CAS 104448-53-5
  TTD Drug ID: DM0195G

Molecule-Related Drug Atlas

Drug(s) Targeting Leukotriene receptor (LTR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
SR-2640	DMFDA4Y	Asthma	CA23	Phase 2	[4]
Ontazolast	DMS8Q7A	Asthma	CA23	Phase 2	[5]
PIRODOMAST	DMC3T2S	Asthma	CA23	Phase 2	[6]
WF-11605	DM57FHW	Bacterial infection	1A00-1C4Z	Phase 1	[7]
SK&F-S-106203	DM2BDAW	Asthma	CA23	Discontinued in Phase 2	[8]
FK-664	DMFGJNW	Cardiac disease	BA00-BE2Z	Discontinued in Phase 2	[9]
SMP-028	DMQSGOD	Asthma	CA23	Discontinued in Phase 1	[10]
NZ-107	DMXJO5F	Asthma	CA23	Discontinued in Phase 1	[11]
ABT-080	DMTYWE9	Asthma	CA23	Discontinued in Phase 1	[12]
BAY-Y-1015	DM0UEKF	Inflammation	1A00-CA43.1	Discontinued in Phase 1	[13]

Drug(s) Targeting Leukotriene CysLT1 receptor (CYSLTR1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Montelukast	DMD157S	Allergic asthma	CA23.0	Approved	[14]
Zafirlukast	DMHNQOG	Asthma	CA23	Approved	[15]
Pranlukast	DMYHDCA	Allergic rhinitis	CA08.0	Approved	[16]
Cinalukast	DMFIC0M	Asthma	CA23	Approved	[17]
KP-496	DMCO8UZ	Asthma	CA23	Phase 2	[18]
BAY-X-7195	DM2XE80	Asthma	CA23	Phase 2	[19]
Masilukast	DMDTI0L	Asthma	CA23	Phase 2	[20]
LM-1507.NA	DMW6VA0	Asthma	CA23	Phase 2	[21]
Iralukast	DMQ3RWN	Asthma	CA23	Phase 2	[22]
YM-57158	DMS31YW	Allergic rhinitis	CA08.0	Phase 1	[23]

Drug(s) Targeting Leukotriene CysLT2 receptor (CYSLTR2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BAY-X-7195	DM2XE80	Asthma	CA23	Phase 2	[19]
AS-35	DMC2WI7	Asthma	CA23	Discontinued in Phase 2	[24]
DS-4574	DM8GZWC	Asthma	CA23	Discontinued in Phase 2	[25]
Sulukast	DMBSLZV	Asthma	CA23	Discontinued in Phase 2	[26]
MDL-43291	DMBIDQX	Asthma	CA23	Terminated	[27]
LY-290154	DMPZ7AO	Asthma	CA23	Terminated	[28]
FPL-55712	DMF1CDK	Asthma	CA23	Terminated	[29]
LTE4	DMCPB0Q	Discovery agent	N.A.	Investigative	[30]
LTC4	DM702WR	Discovery agent	N.A.	Investigative	[31]
LTD4	DMIUZX3	Discovery agent	N.A.	Investigative	[31]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Leukotriene CysLT1 receptor (CYSLTR1)	TTGKOY9	CLTR1_HUMAN	Antagonist	[2]
Leukotriene CysLT2 receptor (CYSLTR2)	TT0PZR5	CLTR2_HUMAN	Antagonist	[2]
Leukotriene receptor (LTR)	TTTWGIX	NOUNIPROTAC	Modulator	[3]

References

• [1] 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).
• [2] Heterogeneity of binding sites for ICI 198,615 in human lung parenchyma. Biochem Pharmacol. 1992 Oct 6;44(7):1411-5.
• [3] In vitro pharmacology of ICI 198,615: a novel, potent and selective peptide leukotriene antagonist. J Pharmacol Exp Ther. 1987 Nov;243(2):548-56.
• [4] Effect of the leukotriene LTD4/LTE4 antagonist, SR 2640, in ulcerative colitis: an open clinical study. Prostaglandins Leukot Essent Fatty Acids. 1991 Mar;42(3):181-4.
• [5] Effects of progesterone and leukotriene receptor antagonists in experimental models of P-glycoprotein-related resistance. Eur J Med Res. 1997 Apr 21;2(4):159-64.
• [6] Antiallergy activity of Sch 37224, a new inhibitor of leukotriene formation. J Pharmacol Exp Ther. 1988 Dec;247(3):997-1003.
• [7] WF11605, an antagonist of leukotriene B4 produced by a fungus. II. Structure determination. J Antibiot (Tokyo). 1992 May;45(5):704-8.
• [8] Pharmacologic and pharmacokinetic profile of SK&F S-106203, a potent, orally active peptidoleukotriene receptor antagonist, in guinea-pig. Pulm Pharmacol. 1991;4(3):177-89.
• [9] US patent application no. 7,175,854, Pharmaceutical preparation comprising an active dispersed on a matrix.
• [10] Effect of SMP-028 on steroidogenesis in rats; mechanism of toxicological events on endocrine organs of rats. Toxicol In Vitro. 2014 Apr;28(3):397-402.
• [11] Effects of NZ-107 on tracheal responses to adenosine in the guinea pig. Jpn J Pharmacol. 1991 May;56(1):79-84.
• [12] An update on the role of leukotrienes in asthma. Curr Opin Allergy Clin Immunol. 2010 February; 10(1): 60-66.
• [13] The effect of leukotriene synthesis inhibitors in models of acute and chronic inflammation. Arthritis Rheum. 1996 Mar;39(3):515-21.
• [14] Protective potential of montelukast against hepatic ischemia/reperfusion injury in rats. J Surg Res. 2010 Mar;159(1):588-94.
• [15] Inhibitory effects of zafirlukast on respiratory bursts of human neutrophils. Drugs Exp Clin Res. 2002;28(4):133-45.
• [16] Beneficial 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.
• [17] Prolonged protection against exercise-induced bronchoconstriction by the leukotriene D4-receptor antagonist cinalukast. J Allergy Clin Immunol. 1997 Feb;99(2):210-5.
• [18] Effects 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.
• [19] 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.
• [20] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [21] Pharmacological 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.
• [22] Pharmacological 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.
• [23] In vitro pharmacologic profile of YM158, a new dual antagonist for LTD4 and TXA2 receptors. J Pharmacol Exp Ther. 1998 Nov;287(2):633-9.
• [24] Inhibition of radiolabeled leukotriene-binding by AS-35 in guinea pig lung membrane fraction. Jpn J Pharmacol. 1992 Apr;58(4):357-64.
• [25] 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.
• [26] 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.
• [27] 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.
• [28] DOI: 10.1021/op060036x
• [29] 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.
• [30] 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.
• [31] 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.