Disease Information

General Information of the Disease (ID: DIS00293)

• Name: Coronary artery disease
• ICD: ICD-11: BA8Z

Type(s) of Resistant Mechanism of This Disease

  DISM: Drug Inactivation by Structure Modification

  IDUE: Irregularity in Drug Uptake and Drug Efflux

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Cilostazol

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ATP-binding cassette sub-family C4 (ABCC4) [1]

• Sensitive Disease: Coronary artery disease [ICD-11: BA8Z.0]
• Molecule Alteration: Function; Inhibition
• Sensitive Drug: Cilostazol
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: JAK2 signaling pathway; Activation; hsa04917
• Cell Pathway Regulation: STAT3 signaling pathway; Activation; hsa04550
• Mechanism Description: Cilostazol has been implicated in a number of other basic pathways including the inhibition of adenosine reuptake, the inhibition of multidrug resistance protein 4, among others. Mouse models of myocardial ischemia reperfusion have associated cilostazol with attenuation of multiple inflammatory markers through activation of PPAR gamma, JAK2, and STAT3 pathways

Key Molecule: ATP-binding cassette sub-family C4 (ABCC4) [1]

• Sensitive Disease: Coronary artery disease [ICD-11: BA8Z.0]
• Molecule Alteration: Function; Inhibition
• Sensitive Drug: Cilostazol
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: JAK2 signaling pathway; Activation; hsa04917
• Cell Pathway Regulation: STAT3 signaling pathway; Activation; hsa04550
• Mechanism Description: Cilostazol has been implicated in a number of other basic pathways including the inhibition of adenosine reuptake, the inhibition of multidrug resistance protein 4, among others. Mouse models of myocardial ischemia reperfusion have associated cilostazol with attenuation of multiple inflammatory markers through activation of PPAR gamma, JAK2, and STAT3 pathways

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Phosphodiesterase III (PDE) [1]

• Sensitive Disease: Coronary artery disease [ICD-11: BA8Z.0]
• Molecule Alteration: Function; Inhibition
• Sensitive Drug: Cilostazol
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: JAK2 signaling pathway; Activation; hsa04917
• Cell Pathway Regulation: STAT3 signaling pathway; Activation; hsa04550
• Mechanism Description: Cilostazol has been implicated in a number of other basic pathways including the inhibition of adenosine reuptake, the inhibition of multidrug resistance protein 4, among others. Mouse models of myocardial ischemia reperfusion have associated cilostazol with attenuation of multiple inflammatory markers through activation of PPAR gamma, JAK2, and STAT3 pathways

Key Molecule: Phosphodiesterase III (PDE) [1]

• Sensitive Disease: Coronary artery disease [ICD-11: BA8Z.0]
• Molecule Alteration: Function; Inhibition
• Sensitive Drug: Cilostazol
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: JAK2 signaling pathway; Activation; hsa04917
• Cell Pathway Regulation: STAT3 signaling pathway; Activation; hsa04550
• Mechanism Description: Cilostazol has been implicated in a number of other basic pathways including the inhibition of adenosine reuptake, the inhibition of multidrug resistance protein 4, among others. Mouse models of myocardial ischemia reperfusion have associated cilostazol with attenuation of multiple inflammatory markers through activation of PPAR gamma, JAK2, and STAT3 pathways

Clopidogrel

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Cytochrome P450 family 2 subfamily C member 19 (CYP2C19) [2]

• Resistant Disease: Coronary artery disease [ICD-11: BA8Z.0]
• Molecule Alteration: SNP; CYP2C19*2
• Resistant Drug: Clopidogrel
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Blood sample; .
• Experiment for Molecule Alteration: Genetic analysis assay
• Experiment for Drug Resistance: Platelet aggregation test assay
• Mechanism Description: Among the 72 patients studied, 32.6% were carriers of CYP2C19*2 loss-of-function allele. This allele was found to be more common but not significantly so from the controls (27.7%). The loss-of-function genotypes (*2/*2 or *2/*1) of CYP2C19 were seen to be significantly higher in clopidogrel semi-responders compared to responders (72.9% vs 34.3%, P = 0.0023, respectively). Similarly, significantly higher frequency of the mutant *2 allele of CYP2C19 was observed in clopidogrel semi-responders than in responders (43.2% vs 21.4%, P = 0.007).

References

• Ref 1: Cilostazol: a Review of Basic Mechanisms and Clinical Uses .Cardiovasc Drugs Ther. 2021 Apr 16. doi: 10.1007/s10557-021-07187-x. Online ahead of print. 10.1007/s10557-021-07187-x
• Ref 2: Association of CYP2C19, CYP3A5 and GPIIb/IIIa gene polymorphisms with Aspirin and Clopidogrel Resistance in a cohort of Indian patients with Coronary Artery Disease .Int J Lab Hematol. 2015 Dec;37(6):809-18. doi: 10.1111/ijlh.12416. Epub 2015 Aug 12. 10.1111/ijlh.12416