Disease Information

General Information of the Disease (ID: DIS00114)

• Name: Multiple sclerosis
• ICD: ICD-11: 8A40

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

Teriflunomide

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ATP-binding cassette sub-family G2 (ABCG2) [1]

• Sensitive Disease: Multiple sclerosis [ICD-11: 8A40.0]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Teriflunomide
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: C57BL/6J cells(Mus musculus (Mouse)); Lymph; Homo sapiens (Human); CVCL_5U84
• In Vivo Model: EAE mice model; Mus musculus
• Experiment for Drug Resistance: Annexin V staining assay
• Mechanism Description: In vitro, intracellular teri concentration in T cells was 2.5-fold higher in abcg2-kO mice than in wt mice. Teri-induced inhibition of T cell proliferation was two fold increased in abcg2-kO cells compared to wt.

Key Molecule: ATP-binding cassette sub-family G2 (ABCG2) [1]

• Sensitive Disease: Multiple sclerosis [ICD-11: 8A40.0]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Teriflunomide
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: C57BL/6J cells(Mus musculus (Mouse)); Lymph; Homo sapiens (Human); CVCL_5U84
• In Vivo Model: EAE mice model; Mus musculus
• Experiment for Drug Resistance: Annexin V staining assay
• Mechanism Description: Pharmacological abcg2 inhibition in T cells from wt mice led to an increase of teri-induced apoptosis (Ko143 vs. DMSO: 3.1-fold, p < 0.05; FTC vs. DMSO: 2.8-fold, p > 0.05).

References

• Ref 1: Functional relevance of the multi-drug transporter abcg2 on teriflunomide therapy in an animal model of multiple sclerosis. J Neuroinflammation. 2020 Jan 8;17(1):9. doi: 10.1186/s12974-019-1677-z.