Drug Information

Drug (ID: DG00327) and It's Reported Resistant Information

Name	Temocapril hydrochloride
Synonyms	Acecol (TN) Click to Show/Hide
Indication	In total 1 Indication(s) Cardiovascular disease [ICD-11: BA00-BE2Z] Approved [1]
Structure
Drug Resistance Disease(s)	Disease(s) with Clinically Reported Resistance for This Drug (1 diseases) Haemorrhage [ICD-11: MG27] [1]
Target	Angiotensin-converting enzyme (ACE)	ACE_HUMAN	[1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula	C23H29ClN2O5S2
IsoSMILES	CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@H]2CS[C@@H](CN(C2=O)CC(=O)O)C3=CC=CS3.Cl
InChI	1S/C23H28N2O5S2.ClH/c1-2-30-23(29)17(11-10-16-7-4-3-5-8-16)24-18-15-32-20(19-9-6-12-31-19)13-25(22(18)28)14-21(26)27;/h3-9,12,17-18,20,24H,2,10-11,13-15H2,1H3,(H,26,27);1H/t17-,18-,20-;/m0./s1
InChIKey	XDDQNOKKZKHBIX-ASBZXGSUSA-N
PubChem CID	443873
ChEBI ID	CHEBI:32190
TTD Drug ID	D02DSZ
DrugBank ID	DB08836

Type(s) of Resistant Mechanism of This Drug

DISM: Drug Inactivation by Structure Modification

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-21: Symptoms/clinical signs/unclassified clinical findings

Click to Show/Hide the Resistance Disease of This Class

Haemorrhage [ICD-11: MG27]

Click to Show/Hide

Drug Resistance Data Categorized by Their Corresponding Mechanisms
Drug Inactivation by Structure Modification (DISM)			Click to Show/Hide
Key Molecule: Liver carboxylesterase 1 (CES1)				[1]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Disease	Haemorrhage [ICD-11: MG27.0]			Disease Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	CaCo2 cells	Colon	Homo sapiens (Human)	CVCL_0025
	IPS cells	Colon	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	qPCR
Experiment for Drug Resistance	Transcellular transport study assay
Mechanism Description	The extraction ratio value of metabolism of temocapril (a CES1 substrate) to temocaprilat in the absence and presence of 500 uM BNPP (a CES inhibitor) in hiPSC-IECs were 4.17 +/- 0.22 (%) and 5.18 +/- 0.30 (%), respectively. In contrast, the extraction ratio in Caco-2 cells was 99.0 +/- 0.1 (%) and decreased to 1.29 +/- 0.07 (%) in the presence of 500 uM BNPP.

References

Ref 1	Application of Intestinal Epithelial Cells Differentiated from Human Induced Pluripotent Stem Cells for Studies of Prodrug Hydrolysis and Drug Absorption in the Small Intestine. Drug Metab Dispos. 2018 Nov;46(11):1497-1506. doi: 10.1124/dmd.118.083246. Epub 2018 Aug 22.