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

General Information of Drug (ID: DMF1CDK)

• Drug Name: FPL-55712 Drug Info
• Synonyms: Fpl-55712; 40786-08-1; 7-((3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxypropoxyl))-4-oxo-8-propyl-4H-chromene-2-carboxy late, sodium salt; CHEMBL267976; 7-[3-(4-Acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxypropoxy]- 4-oxo-8-propyl-4H-1-benzopyran-2-carboxylic acid sodium salt; 4H-1-Benzopyran-2-carboxylic acid, 7-(3-(4-acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxypropoxy)-4-oxo-8-propyl-, monosodium salt; fpl55712; SCHEMBL1890293; AOB5208; ZDEVPOBNLIVGFA-UHFFFAOYSA-M; MFCD00068619; LS-186693; FT-0639668; FPL-55712, &gt

Indication

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

• Cross-matching ID:
  PubChem CID: 23662025
  CAS Number: CAS 40786-08-1
  TTD Drug ID: DMF1CDK

Molecule-Related Drug Atlas

Drug(s) Targeting Leukotriene CysLT1 receptor (CYSLTR1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Montelukast	DMD157S	Allergic asthma	CA23.0	Approved	[4]
Zafirlukast	DMHNQOG	Asthma	CA23	Approved	[5]
Pranlukast	DMYHDCA	Allergic rhinitis	CA08.0	Approved	[6]
Cinalukast	DMFIC0M	Asthma	CA23	Approved	[7]
KP-496	DMCO8UZ	Asthma	CA23	Phase 2	[8]
BAY-X-7195	DM2XE80	Asthma	CA23	Phase 2	[9]
Masilukast	DMDTI0L	Asthma	CA23	Phase 2	[10]
LM-1507.NA	DMW6VA0	Asthma	CA23	Phase 2	[11]
Iralukast	DMQ3RWN	Asthma	CA23	Phase 2	[12]
YM-57158	DMS31YW	Allergic rhinitis	CA08.0	Phase 1	[13]

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	[9]
AS-35	DMC2WI7	Asthma	CA23	Discontinued in Phase 2	[14]
DS-4574	DM8GZWC	Asthma	CA23	Discontinued in Phase 2	[15]
Sulukast	DMBSLZV	Asthma	CA23	Discontinued in Phase 2	[16]
ICI-198615	DM0195G	Asthma	CA23	Terminated	[17]
MDL-43291	DMBIDQX	Asthma	CA23	Terminated	[18]
LY-290154	DMPZ7AO	Asthma	CA23	Terminated	[19]
LTE4	DMCPB0Q	Discovery agent	N.A.	Investigative	[20]
LTC4	DM702WR	Discovery agent	N.A.	Investigative	[21]
LTD4	DMIUZX3	Discovery agent	N.A.	Investigative	[21]

Drug(s) Affected By Polyunsaturated fatty acid 5-lipoxygenase (ALOX5)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Meclofenamic acid	DM05FXR	Ankylosing spondylitis	FA92.0	Approved	[22]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[23]
SPI-1005	DM6XFHS	Reperfusion injury	ND56.Z	Approved	[24]
Fructose	DM43AN2	Vomiting	MD90	Approved	[25]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[26]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[27]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[28]
Loratadine	DMF3AN7	Allergy	4A80-4A85	Approved	[29]
Zoledronate	DMIXC7G	Adenocarcinoma	2D40	Approved	[30]
Niclosamide	DMJAGXQ	Cestodes infection	1F70-1F76	Approved	[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	Modulator	[2]
Leukotriene CysLT2 receptor (CYSLTR2)	TT0PZR5	CLTR2_HUMAN	Modulator	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Polyunsaturated fatty acid 5-lipoxygenase (ALOX5)	OT7FOIK2	LOX5_HUMAN	Gene/Protein Processing	[3]

References

• [1] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000089)
• [2] 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.
• [3] Species difference of 5-lipoxygenase derived from polymorphonuclear leukocytes on sensitivity to drugs. Jpn J Pharmacol. 1989 May;50(1):37-46.
• [4] Protective potential of montelukast against hepatic ischemia/reperfusion injury in rats. J Surg Res. 2010 Mar;159(1):588-94.
• [5] Inhibitory effects of zafirlukast on respiratory bursts of human neutrophils. Drugs Exp Clin Res. 2002;28(4):133-45.
• [6] 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.
• [7] Prolonged protection against exercise-induced bronchoconstriction by the leukotriene D4-receptor antagonist cinalukast. J Allergy Clin Immunol. 1997 Feb;99(2):210-5.
• [8] 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.
• [9] 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.
• [10] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] Inhibition of radiolabeled leukotriene-binding by AS-35 in guinea pig lung membrane fraction. Jpn J Pharmacol. 1992 Apr;58(4):357-64.
• [15] 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.
• [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.
• [17] Heterogeneity of binding sites for ICI 198,615 in human lung parenchyma. Biochem Pharmacol. 1992 Oct 6;44(7):1411-5.
• [18] 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.
• [19] DOI: 10.1021/op060036x
• [20] 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.
• [21] 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.
• [22] Meclofenamate sodium is an inhibitor of both the 5-lipoxygenase and cyclooxygenase pathways of the arachidonic acid cascade in vitro. Prostaglandins Leukot Med. 1986 Aug;23(2-3):229-38.
• [23] Resveratrol prevents apoptosis in K562 cells by inhibiting lipoxygenase and cyclooxygenase activity. Eur J Biochem. 1999 Oct 1;265(1):27-34.
• [24] Molecular actions of ebselen--an antiinflammatory antioxidant. Gen Pharmacol. 1995 Oct;26(6):1153-69.
• [25] Non-nutritional sweeteners effects on endothelial vascular function. Toxicol In Vitro. 2020 Feb;62:104694. doi: 10.1016/j.tiv.2019.104694. Epub 2019 Oct 23.
• [26] Immediate up-regulation of the calcium-binding protein S100P and its involvement in the cytokinin-induced differentiation of human myeloid leukemia cells. Biochim Biophys Acta. 2005 Sep 10;1745(2):156-65.
• [27] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [28] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [29] Cetirizine and loratadine-based antihistamines with 5-lipoxygenase inhibitory activity. Bioorg Med Chem Lett. 2004 Nov 15;14(22):5591-4.
• [30] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [31] Mitochondrial uncoupling reveals a novel therapeutic opportunity for p53-defective cancers. Nat Commun. 2018 Sep 26;9(1):3931.