Details of the Drug

General Information of Drug (ID: DMCF6SX)

Drug Name

TAK-491

Synonyms

TAK 491

Indication

Disease Entry	ICD 11	Status	REF
Hypertension	BA00-BA04	Phase 3	[1]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 1

Molecular Weight (mw)

568.5

Topological Polar Surface Area (xlogp)

4.9

Rotatable Bond Count (rotbonds)

10

Hydrogen Bond Donor Count (hbonddonor)

1

Hydrogen Bond Acceptor Count (hbondacc)

10

Chemical Identifiers

Formula: C30H24N4O8
IUPAC Name: (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-ethoxy-3-[[4-[2-(5-oxo-4H-1,2,4-oxadiazol-3-yl)phenyl]phenyl]methyl]benzimidazole-4-carboxylate
Canonical SMILES: CCOC1=NC2=CC=CC(=C2N1CC3=CC=C(C=C3)C4=CC=CC=C4C5=NOC(=O)N5)C(=O)OCC6=C(OC(=O)O6)C
InChI: InChI=1S/C30H24N4O8/c1-3-38-28-31-23-10-6-9-22(27(35)39-16-24-17(2)40-30(37)41-24)25(23)34(28)15-18-11-13-19(14-12-18)20-7-4-5-8-21(20)26-32-29(36)42-33-26/h4-14H,3,15-16H2,1-2H3,(H,32,33,36)
InChIKey: QJFSABGVXDWMIW-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 135409642
ChEBI ID: CHEBI:68845
CAS Number: 863031-21-4
TTD ID: D0A2RA
ACDINA ID: D00055

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Angiotensin II receptor type-1 (AGTR1)	TT8DBY3	AGTR1_HUMAN	Modulator	[2]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Molecular Expression Atlas of This Drug

The Studied Disease

Hypertension

ICD Disease Classification

BA00-BA04

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Angiotensin II receptor type-1 (AGTR1)	DTT	AGTR1	8.95E-01	1.34E-02	0.07

Molecular Expression Atlas (MEA)

MEA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as TAK-491

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Aliskiren	DM1BV7W	Major	Increased risk of hyperkalemia by the combination of TAK-491 and Aliskiren.	Hypertension [BA00-BA04]	[11]
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Coadministration of a Drug Treating the Disease Different from TAK-491 (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
OPC-34712	DMHG57U	Moderate	Additive hypotensive effects by the combination of TAK-491 and OPC-34712.	Depression [6A70-6A7Z]	[12]
Ozanimod	DMT6AM2	Moderate	Additive hypotensive effects by the combination of TAK-491 and Ozanimod.	Multiple sclerosis [8A40]	[13]
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Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Fumaric acid	E00420	444972	Acidulant; Antioxidant; Complexing agent; Flavoring agent; Solubilizing agent
Mannitol	E00103	6251	Diluent; Flavoring agent; Lyophilization aid; Plasticizing agent; Tonicity agent
Carmellose sodium	E00625	Not Available	Disintegrant
Magnesium stearate	E00208	11177	lubricant
Sodium hydroxide	E00234	14798	Alkalizing agent
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Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Azilsartan medoxomil 40 mg tablet	40 mg	Oral Tablet	Oral
Azilsartan medoxomil 80 mg tablet	80 mg	Oral Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1	ClinicalTrials.gov (NCT02480764) TAK-491 (Azilsartan Medoxomil) Compared to Valsartan in Chinese Participants With Hypertension.
2	2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
3	Radioligand binding assays: application of [(125)I]angiotensin II receptor binding. Methods Mol Biol. 2009;552:131-41.
4	Mechanism of diastolic stiffening of the failing myocardium and its prevention by angiotensin receptor and calcium channel blockers. J Cardiovasc Pharmacol. 2009 Jul;54(1):47-56.
5	Candesartan: widening indications for this angiotensin II receptor blocker Expert Opin Pharmacother. 2009 Aug;10(12):1995-2007.
6	Deletion of angiotensin II type I receptor reduces hepatic steatosis. J Hepatol. 2009 Jun;50(6):1226-35.
7	The amino-terminus of angiotensin II contacts several ectodomains of the angiotensin II receptor AT1. J Med Chem. 2010 Mar 11;53(5):2063-75.
8	Identification of a potent, selective, and orally active leukotriene a4 hydrolase inhibitor with anti-inflammatory activity. J Med Chem. 2008 Jul 24;51(14):4150-69.
9	Tasosartan, enoltasosartan, and angiotensin II receptor blockade: the confounding role of protein binding. J Pharmacol Exp Ther. 2000 Nov;295(2):649-54.
10	Clinical profile of eprosartan: a different angiotensin II receptor blocker. Cardiovasc Hematol Agents Med Chem. 2008 Oct;6(4):253-7.
11	Health Canada "Potential risks of cardiovascular and renal adverse events in patients with type 2 diabetes treated with aliskiren (RASILEZ) or aliskiren/hydrochlorothiazide (RASILEZ HCT)." .
12	Aronowitz JS, Chakos MH, Safferman AZ, Lieberman JA "Syncope associated with the combination of clozapine and enalapril." J Clin Psychopharmacol 14 (1994): 429-30. [PMID: 7884028]
13	Ban TA "Drug interactions with psychoactive drugs." Dis Nerv Syst 36 (1975): 164-6. [PMID: 1116424]