Drug Information

Drug (ID: DG00102) and It's Reported Resistant Information

• Name: Teriflunomide
• Indication:
  In total 4 Indication(s)
  Hyperlipoproteinaemia [ICD-11: 5C80]; Approved; [1]
  Multiple sclerosis [ICD-11: 8A40]; Approved; [1]
  Rheumatoid arthritis [ICD-11: FA20]; Phase 3; [1]
  Hepatitis virus infection [ICD-11: 1E50-1E51]; Phase 1; [1]
• Target: Dihydroorotate dehydrogenase (DHODH); PYRD_HUMAN; [1]
• Target: HMG-CoA reductase (HMGCR); HMDH_HUMAN; [1]
• Target: Plasmodium Dihydroorotate dehydrogenase (Malaria DHOdehase); PYRD_PLAF7; [1]
• Formula: C12H9F3N2O2
• IsoSMILES: C/C(=C(\\C#N)/C(=O)NC1=CC=C(C=C1)C(F)(F)F)/O
• InChI: 1S/C12H9F3N2O2/c1-7(18)10(6-16)11(19)17-9-4-2-8(3-5-9)12(13,14)15/h2-5,18H,1H3,(H,17,19)/b10-7-
• InChIKey: UTNUDOFZCWSZMS-YFHOEESVSA-N
• PubChem CID: 54684141
• ChEBI ID: CHEBI:68540
• TTD Drug ID: D07QFP
• VARIDT ID: DR00092
• DrugBank ID: DB08880

Type(s) of Resistant Mechanism of This Drug

  IDUE: Irregularity in Drug Uptake and Drug Efflux

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-08: Nervous system diseases

Multiple sclerosis [ICD-11: 8A40]

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]

• Molecule Alteration: Expression; Down-regulation
• Sensitive Disease: Multiple sclerosis [ICD-11: 8A40.0]
• 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]

• Molecule Alteration: Expression; Down-regulation
• Sensitive Disease: Multiple sclerosis [ICD-11: 8A40.0]
• 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.