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IDH 2 Inhibitor

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IDH 2 Inhibitor, Isocitrate Dehydrogenase 2 Inhibitor, Enasidenib, Idhifa

  • See Also
  1. IDH 1 Inhibitor
  2. Small Molecule Inhibitor-Mediated Chemotherapy
  3. Chemotherapy
  • Indications
  1. Acute Myelogenous Leukemia (IDH1/2+ new or advanced/refractory)
  • Mechanism
  1. Isocitrate Dehydrogenase (IDH)
    1. Isocitrate Dehydrogenase is a cytoplasmic enzyme that decarboxylating isocitrate to alpha ketoglutarate
    2. Rate limiting step of the TCA Cycle (Kreb Cycle)
    3. Isocitrate Dehydrogenase (IDH) has 3 forms with the same activity (the first 2 are associated with cancers)
      1. IDH1 is found in cytoplasm (and encoded by gene 2q33)
      2. IDH2 is found in mitochondria (and encoded by gene 15q26)
  2. IDH2 Mutations
    1. Associated with Acute Myelogenous Leukemia (similar to IDH1)
  • Medications
  1. Enasidenib (Idhifa)
  • Dosing
  1. See other references for disease specific dosing protocols
  • Safety
  1. Avoid in Lactation
    1. Avoid Breast Feeding for an additional one month after completing Enasidenib
  2. Avoid in pregnancy (all trimesters, pregnancy category X)
    1. Use reliable Contraception
  • Adverse Effects
  1. Edema
  2. Hepatotoxicity
  3. Prolonged QTc
  4. Myelosuppression
  5. Differentiation Syndrome
    1. Presents with fever and Dyspnea
    2. Signs include Pulmonary Infiltrates, Pleural Effusions, Pericardial Effusions, weight gain, Cardiomyopathy, Hypotension
  • Resources
  1. Enasidenib (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a5b4cdf0-3fa8-4c6c-80f6-8d8a00e3a5b6
  • References
  1. Chen (2023) Clin Epigenetics 15(1):113 +PMID: 37434249 [PubMed]