1. CPI-613(Devimistat ) is an E1 pyruvate dehydrogenase (PDH) modulator that prevents cancer cells from metabolizing glucose for energy. CPI-613 has been granted orphan drug status by the US FDA for pancreatic cancer.
CPI-613(Devimistat ) is a first in class agent that targets mitochondrial metabolism through inhibition of pyruvate dehydrogenase and a-ketogluterate dehydrogenase.
2. CPI-613(Devimistat ) is a lipoate derivative synthesized to be catalytically inert but to potentially mimic lipoate catalytic intermediates. The drug is in phase II of clinical trials for the treatment of Myelodysplastic syndromes; Pancreatic cancer; Small cell lung cancer; Solid tumors; Bile duct cancer; Acute Myeloid leukemia. The mechanism of CPI-613(Devimistat ) action can be explained by (I) inhibition of tumor cell pyruvate dehydrogenase complex (PDC) through activation of pyruvate dehydrogenase kinases leading to inactivating phosphorylation of the E1alpha-subunit of PDC; and (II) inhibition of alpha-ketoglutarate dehydrogenase.
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