Disease Information

General Information of the Disease (ID: DIS00140)

• Name: Haemorrhage
• ICD: ICD-11: MG27

Type(s) of Resistant Mechanism of This Disease

  DISM: Drug Inactivation by Structure Modification

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Temocapril hydrochloride

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Liver carboxylesterase 1 (CES1) [1]

• Resistant Disease: Haemorrhage [ICD-11: MG27.0]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Temocapril hydrochloride
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: CaCo2 cells; Colon; Homo sapiens (Human); CVCL_0025
• In Vitro Model: 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.