Disease Information

General Information of the Disease (ID: DIS00122)

• Name: Cardiac arrhythmia
• ICD: ICD-11: BC9Y

Type(s) of Resistant Mechanism of This Disease

  IDUE: Irregularity in Drug Uptake and Drug Efflux

Drug Resistance Data Categorized by Drug

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

Verapamil

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ATP-binding cassette sub-family B5 (ABCB5) [1]

• Sensitive Disease: Arrhythmia [ICD-11: BC9Y.0]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Verapamil
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF-7/DX1 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: Sf9 cells; Ovary; Homo sapiens (Human); CVCL_0549
• In Vitro Model: HCMEC/D3 cells; Brain; Homo sapiens (Human); CVCL_U985
• In Vivo Model: Male Sprague-Dawley Rats Brain Capillary Isolation; Mus musculus
• Mechanism Description: In P-gp overexpressing cells and in human brain capillary endothelial hCMEC/D3 cells, the dimer with the shortest tether length (QT2C2) was the most potent inhibitor showing >80-fold better inhibition of P-gp-mediated transport than monomeric QT. QT2C2Me2 increased the accumulation of the P-gp substrate verapamil in rat brain in situ three times more than QT.

References

• Ref 1: Reversible dimers of the atypical antipsychotic quetiapine inhibit p-glycoprotein-mediated efflux in vitro with increased binding affinity and in situ at the blood-brain barrier. ACS Chem Neurosci. 2014 Apr 16;5(4):305-17. doi: 10.1021/cn4002329. Epub 2014 Feb 7.