tcsc2462 Mdivi-1

Mdivi-1 a selective cell-permeable inhibitor of mitochondrial division dynamin-related GTPase (DRP1) and mitochondrial division Dynamin I (Dnm1).

In Vitro: Mdivi-1 inhibits Dnm1 GTPase activity in a dose-dependent manner, with an estimated EC₅₀ of 1-10 μM. Mdivi-1 increases the apparent K_0.5 for GTP, lowers the apparent V_max for GTP hydrolysis, and causes an increase in the Hill coefficient observed for GTP in the Dnm1 GTP hydrolysis reaction^[1]. Cells treated with mdivi-1 display decreased cytochrome c release and a reduced rate of phosphatidylserine exposure on their surface following apoptosis induction, consistent with an inhibition of apoptosis and with previous studies using other strategies to compromise DRP1 activity^[2]. Mdivi-1 results in apoptotic cell death in ischemic retina^[3].

In Vivo: The mitochondrial division DRP, Dnm1, is the target of mdivi-1 in vivo. Mdivi-1 quantitatively blocks GMPPCP- dependent Dnm1 self-assembly in a concentration range similar to its effects on mitochondrial division in vivo^[1]. Mdivi-1 (50 mg/kg, i.p.) significantly decreases GFAP protein expression in the normal mouse retina^[3].