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

General Information of Drug (ID: DM2ZYX9)

• Drug Name: Pradaxa Drug Info
• Synonyms: Dabigatran etexilate mesylate; 872728-81-9; XETBXHPXHHOLOE-UHFFFAOYSA-N; CP0128; FT-0660872; ethyl 3-[(2-{[4-(hexyloxycarbonylamino-imino-methyl)-phenylamino]-methyl}-1-methyl-1h-benzimidazole-5-carbonyl)-pyridin-2-yl-amino]-propionate methanesulphonate; 1-methyl-2-[N-[4-(N-n-hexyloxycarbonylamidino)phenyl]-amino-methyl]-benzimidazol-5-yl-carboxylic acid-N-(2-pyridyl)-N-(2-ethoxycarbonylethyl)-amide mesylate

Indication

Disease Entry	ICD 11	Status	REF
Stroke	8B20	Phase 3	[1]

• Cross-matching ID:
  PubChem CID: 11434065
  CAS Number: CAS 872728-81-9
  TTD Drug ID: DM2ZYX9
  INTEDE Drug ID: DR1875

Molecule-Related Drug Atlas

Drug(s) Metabolized By Carboxylesterase 1 (CES1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Irinotecan	DMP6SC2	Adenocarcinoma	2D40	Approved	[3]
Enalapril	DMNFUZR	Congestive heart failure	BD10	Approved	[4]
Candesartan	DMRK8OT	Chronic heart failure	BD1Z	Approved	[5]
Salbutamol	DMN9CWF	Acute asthma	CA23	Approved	[6]
Methylphenidate	DM7SJD6	Attention deficit hyperactivity disorder	6A05.Z	Approved	[7]
PSI-7977	DMLSUWZ	HCV 1-6 infection	1E51	Approved	[8]
Rufinamide	DMWE60C	Epilepsy	8A60-8A68	Approved	[9]
Dexmethylphenidate	DMUQE2A	Attention deficit hyperactivity disorder	6A05.Z	Approved	[10]
MK-4827	DMLYGH4	Ovarian cancer	2C73	Phase 3	[11]
Dabigatran etexilate	DMRDZ4X	Venous thromboembolism	BD72	Phase 3	[12]

Drug(s) Metabolized By Carboxylesterase 2 (CES2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Irinotecan	DMP6SC2	Adenocarcinoma	2D40	Approved	[13]
Dexamethasone	DMMWZET	Acute adrenal insufficiency		Approved	[14]
Rufinamide	DMWE60C	Epilepsy	8A60-8A68	Approved	[9]
Dabigatran etexilate	DMRDZ4X	Venous thromboembolism	BD72	Phase 3	[12]

Molecular Interaction Atlas of This Drug

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Carboxylesterase 1 (CES1)	DEB30C5	EST1_HUMAN	Substrate	[2]
Carboxylesterase 2 (CES2)	DETHCPD	EST2_HUMAN	Substrate	[2]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] Conventional liquid chromatography/triple quadrupole mass spectrometry based metabolite identification and semi-quantitative estimation approach in the investigation of in vitro dabigatran etexilate metabolism. Anal Bioanal Chem. 2013 Feb;405(5):1695-704.
• [3] 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.
• [4] 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.
• [5] Different hydrolases involved in bioactivation of prodrug-type angiotensin receptor blockers: carboxymethylenebutenolidase and carboxylesterase 1. Drug Metab Dispos. 2013 Nov;41(11):1888-95.
• [6] 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.
• [7] Methylphenidate is stereoselectively hydrolyzed by human carboxylesterase CES1A1. J Pharmacol Exp Ther. 2004 Aug;310(2):469-76.
• [8] Mechanism of activation of PSI-7851 and its diastereoisomer PSI-7977. J Biol Chem. 2010 Nov 5;285(45):34337-47.
• [9] Investigation of the metabolism of rufinamide and its interaction with valproate. Drug Metab Lett. 2011 Dec;5(4):280-9.
• [10] Dexmethylphenidate hydrochloride in the treatment of attention deficit hyperactivity disorder. Neuropsychiatr Dis Treat. 2006 Dec;2(4):467-73.
• [11] Summary of FDA-approved anticancer cytotoxic drugs at May 2019.
• [12] Pharmacogenomics of novel direct oral anticoagulants: newly identified genes and genetic variants. J Pers Med. 2019 Jan 17;9(1). pii: E7.
• [13] Hydrolysis of irinotecan and its oxidative metabolites, 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino] carbonyloxycamptothecin and 7-ethyl-10-[4-(1-piperidino)-1-amino]-carbonyloxycamptothecin, by human carboxylesterases CES1A1, CES2, and a newly expressed carboxylesterase isoenzyme, CES3. Drug Metab Dispos. 2004 May;32(5):505-11.
• [14] In vitro metabolism of dexamethasone cipecilate, a novel synthetic corticosteroid, in human liver and nasal mucosa. Xenobiotica. 2011 Oct;41(10):874-84.