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devimistat + metformin
- Development stage
- Unknown
- Lead developer
- Cornerstone Pharmaceuticals
- Modality
- Small Molecules
- Administration
- Intravenous, Oral
01
Overview
Devimistat (CPI-613) is a first-in-class small molecule lipoate analog that targets the mitochondrial tricarboxylic acid (TCA) cycle. It selectively inhibits the pyruvate dehydrogenase (PDH) and alpha-ketoglutarate dehydrogenase (KGDH) complexes, which are essential for the energy metabolism of cancer cells. By disrupting these enzymes, devimistat induces metabolic stress and cell death in malignant cells. In the context of relapsed or refractory acute myeloid leukemia (AML) and granulocytic sarcoma, devimistat is being evaluated in combination with metformin. Metformin, a biguanide, is hypothesized to synergize with devimistat by inhibiting mitochondrial complex I, further compromising the bioenergetic capacity of the leukemia cells. This combination therapy is currently being investigated in a Phase 2 pilot study led by Wake Forest University Health Sciences.
- Other names
- CPI-613 + metformindevimistat + metformin
02
Targets
PDH (Pyruvate dehydrogenase complex)GSEC (Gamma-Secretase Complex)OGDH (Dihydrolipoamide S-succinyltransferase)HMGB1 (High mobility group protein B1)ND1 (Mitochondrial electron transport chain complex I)DHFR (Dihydrofolate reductase)
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