Drug Information

Drug (ID: DG01707) and It's Reported Resistant Information

• Name: AGI-5198/Olaparib
• Synonyms: AGI-5198/Olaparib
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Sarcoma [ICD-11: 2C35]; [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

Sarcoma [ICD-11: 2C35]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Oxalosuccinate decarboxylase (IDH1) [1]

• Resistant Disease: Sarcoma [ICD-11: 2C35.0]
• Molecule Alteration: Missense mutation; p.R132C (c.394C>T)
• Wild Type Structure: Method: X-ray diffraction; Resolution: 1.93 Å; PDB: 5GIR
• Mutant Type Structure: Method: X-ray diffraction; Resolution: 2.20 Å; PDB: 6IO0

RMSD: 1.64; TM score: 0.30204; Amino acid change: R132C

• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: IDH2 cells; Ovary; Homo sapiens (Human); CVCL_D3DY
• In Vitro Model: IDH1 cells; Ovary; Homo sapiens (Human); CVCL_D3DY
• 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.