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

General Information of Drug (ID: DM1S489)

• Drug Name: E6005 Drug Info
• Synonyms: Lotamilast; 947620-48-6; E6005; E-6005; UNII-TO043KKB9C; TO043KKB9C; Methyl 4-((3-(6,7-dimethoxy-2-(methylamino)quinazolin-4-yl)phenyl)carbamoyl)benzoate; RVT-501; Methyl 4-({3-[6,7-dimethoxy-2-(methylamino)quinazolin-4-yl]phenyl}carbamoyl)benzoate; Lotamilast [USAN]; SCHEMBL369445; CHEMBL3989967; MolPort-046-033-604; BCP25249; EX-A1382; ZINC113676839; AKOS027337123; SB16962; DB12776; CS-7517; (Methyl 4-(((3-(6,7-dimethoxy-2-(methylamino)quinazolin-4-yl)phenyl(amino)carbonyl)benzoate; HY-12740; AS-52366; Benzoic acid, 4-(((3-(6,7

Indication

Disease Entry	ICD 11	Status	REF
Atopic dermatitis	EA80	Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 24864553
  CAS Number: CAS 947620-48-6
  TTD Drug ID: DM1S489
  INTEDE Drug ID: DR1841

Molecule-Related Drug Atlas

Drug(s) Targeting Phosphodiesterase 4 (PDE4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Apremilast	DMTWS9E	Psoriasis vulgaris	EA90	Approved	[4]
Oxtriphylline	DMLHSE3	Cough	MD12	Approved	[5]
Roflumilast	DMPGHY8	Asthma	CA23	Approved	[6]
Ibudilast	DM4LSPN	Castleman's disease	4B2Y	Approved	[7]
crisaborole	DMNVKU6	Atopic dermatitis	EA80	Approved	[8]
Arofylline	DM84AD1	Chronic obstructive pulmonary disease	CA22	Phase 3	[9]
ARQ-151	DML61S4	Atopic dermatitis	EA80	Phase 3	[10]
SUN13834	DMPK34E	Gram-positive bacterial infection	1B74-1G40	Phase 2	[11]
ONO-6126	DMRT28X	Chronic obstructive pulmonary disease	CA22	Phase 2	[9]
IC-485	DMB1UYV	Chronic obstructive pulmonary disease	CA22	Phase 2	[9]

Drug(s) Metabolized By Carboxylesterase 1 (CES1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Irinotecan	DMP6SC2	Adenocarcinoma	2D40	Approved	[12]
Enalapril	DMNFUZR	Congestive heart failure	BD10	Approved	[13]
Candesartan	DMRK8OT	Chronic heart failure	BD1Z	Approved	[14]
Salbutamol	DMN9CWF	Acute asthma	CA23	Approved	[15]
Methylphenidate	DM7SJD6	Attention deficit hyperactivity disorder	6A05.Z	Approved	[16]
PSI-7977	DMLSUWZ	HCV 1-6 infection	1E51	Approved	[17]
Rufinamide	DMWE60C	Epilepsy	8A60-8A68	Approved	[18]
Dexmethylphenidate	DMUQE2A	Attention deficit hyperactivity disorder	6A05.Z	Approved	[19]
MK-4827	DMLYGH4	Ovarian cancer	2C73	Phase 3	[20]
Dabigatran etexilate	DMRDZ4X	Venous thromboembolism	BD72	Phase 3	[21]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Phosphodiesterase 4 (PDE4)	TTV5CGO	NOUNIPROTAC	Inhibitor	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Carboxylesterase 1 (CES1) Main DME	DEB30C5	EST1_HUMAN	Substrate	[3]

References

• [1] ClinicalTrials.gov (NCT01461941) A Phase 2 Study of E6005 in Patients With Atopic Dermatitis. U.S. National Institutes of Health.
• [2] Antipruritic effect of the topical phosphodiesterase 4 inhibitor E6005 ameliorates skin lesions in a mouse atopic dermatitis model. J Pharmacol Exp Ther. 2013 Jul;346(1):105-12.
• [3] Safety and efficacy of topical E6005, a phosphodiesterase 4 inhibitor, in Japanese adult patients with atopic dermatitis: results of a randomized, vehicle-controlled, multicenter clinical trial. J Dermatol. 2014 Jul;41(7):577-85.
• [4] Highly selective phosphodiesterase 4 inhibitors for the treatment of allergic skin diseases and psoriasis. Inflamm Allergy Drug Targets. 2007 Mar;6(1):17-26.
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [6] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [7] Therapeutic targeting of 3',5'-cyclic nucleotide phosphodiesterases: inhibition and beyond. Nat Rev Drug Discov. 2019 Oct;18(10):770-796.
• [8] 2016 FDA drug approvals. Nat Rev Drug Discov. 2017 Feb 2;16(2):73-76.
• [9] Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91.
• [10] Trial of Roflumilast Cream for Chronic Plaque Psoriasis. N Engl J Med. 2020 Jul 16;383(3):229-239.
• [11] Ocular hypotension induced by topical dopaminergic drugs and phosphodiesterase inhibitors. Eur J Pharmacol. 1994 Jun 2;258(1-2):85-94.
• [12] Irinotecan and its active metabolite, SN-38: review of bioanalytical methods and recent update from clinical pharmacology perspectives. Biomed Chromatogr. 2010 Jan;24(1):104-23.
• [13] Absorption and cleavage of enalapril, a carboxyl ester prodrug, in the rat intestine: in vitro, in situ intestinal perfusion and portal vein cannulation models. Biopharm Drug Dispos. 2015 Sep;36(6):385-397.
• [14] Different hydrolases involved in bioactivation of prodrug-type angiotensin receptor blockers: carboxymethylenebutenolidase and carboxylesterase 1. Drug Metab Dispos. 2013 Nov;41(11):1888-95.
• [15] Effect of carboxylesterase 1 c.428G>A single nucleotide variation on the pharmacokinetics of quinapril and enalapril. Br J Clin Pharmacol. 2015 Nov;80(5):1131-8.
• [16] Methylphenidate is stereoselectively hydrolyzed by human carboxylesterase CES1A1. J Pharmacol Exp Ther. 2004 Aug;310(2):469-76.
• [17] Mechanism of activation of PSI-7851 and its diastereoisomer PSI-7977. J Biol Chem. 2010 Nov 5;285(45):34337-47.
• [18] Investigation of the metabolism of rufinamide and its interaction with valproate. Drug Metab Lett. 2011 Dec;5(4):280-9.
• [19] Dexmethylphenidate hydrochloride in the treatment of attention deficit hyperactivity disorder. Neuropsychiatr Dis Treat. 2006 Dec;2(4):467-73.
• [20] Summary of FDA-approved anticancer cytotoxic drugs at May 2019.
• [21] Pharmacogenomics of novel direct oral anticoagulants: newly identified genes and genetic variants. J Pers Med. 2019 Jan 17;9(1). pii: E7.