Biguanide-based mammalian respiratory complex I inhibitor that exhibits significantly higher potency than metformin and phenformin.
IM1761092 (IM1092) is a biguanide-based mammalian respiratory complex I inhibitor that reduces cellular oxygen consumption (IC50 = 3.6 μM post 6h treatment; HEPG2 C3A cells) and exhibits significantly higher potency than metformin and phenformin (by 10- to 2000-fold depending on the conditions) using bovine heart mitochondrial membrane preparations (IM1092/phenformin/metformin IC50 = 32 μM/3.8 mM/99 mM against active complex I, 4 μM/131 μM/33 mM against deactive complex I).
Science (New York, N.Y.), 379(6630), 351-357 (2023-01-27)
The molecular mode of action of biguanides, including the drug metformin, which is widely used in the treatment of diabetes, is incompletely characterized. Here, we define the inhibitory drug-target interaction(s) of a model biguanide with mammalian respiratory complex I by
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