Drug (ID: DG01707) and It's Reported Resistant Information
Name
AGI-5198/Olaparib
Synonyms
AGI-5198/Olaparib
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Drug Resistance Disease(s)
Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
Sarcoma [ICD-11: 2C35]
[1]
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
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Sarcoma [ICD-11: 2C35]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: Oxalosuccinate decarboxylase (IDH1) [1]
Molecule Alteration Missense mutation
p.R132C (c.394C>T)
Resistant Disease Sarcoma [ICD-11: 2C35.0]
Experimental Note Identified from the Human Clinical Data
In Vitro Model IDH2 cells N.A. Homo sapiens (Human) N.A.
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.

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