Drug Information

Drug (ID: DG01881) and It's Reported Resistant Information

• Name: PARP inhibitors
• Synonyms: PARP inhibitors
• Target: .; NOUNIPROTAC; [1]

Type(s) of Resistant Mechanism of This Drug

  EADR: Epigenetic Alteration of DNA, RNA or Protein

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Oxalosuccinate decarboxylase (IDH1) [1]

• Molecule Alteration: Missense mutation; p.R132H (c.395G>A)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: IDH2 cells; N.A.; Homo sapiens (Human); N.A.
• In Vitro Model: IDH1 cells; N.A.; Homo sapiens (Human); N.A.
• In Vivo Model: Female athymic nu/nu mouse PDX model; Mus musculus
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: The oncometabolite, 2-hydroxyglutarate, renders IDH1/2 mutant cancer cells deficient in homologous recombination and confers vulnerability to synthetic lethal targeting with PARP inhibitors.

References

• Ref 1: 2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivitySci Transl Med. 2017 Feb 1;9(375):eaal2463. doi: 10.1126/scitranslmed.aal2463.