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POSH-IN-2 (MIDI), a mitochondrial division inhibitor, is a DRP1 inhibitor that potently blocks mitochondrial fragmentation induced by cellular stresses and genetic mitochondrial lesions. POSH-IN-2 covalently interacts with DRP1-C367 to target DRP1 interaction with multiple receptors[1].

Mitochondrial fission inhibitor th at blocks DRP1 recruitment to mitochondria.



DRP1 Inhibitor MIDI is a cell-permeablesymmetrical pyridinyl-propenone compound th at acts as a potenttime-dependent mitochondrial fission inhibitor (0.5 - 2 μM) and functionally mimics DRP1 knockout. MIDI is shown to covalently interact with DRP1-C367 and disrupt DRP1 interaction with its mitochondrial receptors MFF and MiD49/51. Blocks stress-induced mitochondrial fragmentation and promotes mitochondrial hyperfusion. MIDI does neither obstruct DRP1 tetramerization nor its GTPase activity. Poorly affects mitochondrial oxygen consumption rate and glycolysis activity.

[1] Jun Yang, et al. Chemical inhibition of mitochondrial fission via targeting the DRP1-receptor interaction. Cell Chem Biol. 2023 Mar 16;30(3):278-294.e11. DOI:10.1016/j.chembiol.2023.02.002