NMac1

NMac1 is an orally active Nm23/NDPK activator. NMac1 directly binds to Nm23-H1 and activates the NDPK activity of recombinant Nm23-H1 with an EC₅₀ of 10.7 uM. NMac1 induces AMPK activation and inhibits mTOR and ERK, leading to mitochondrial OXPHOS dysregulation and suppressing mitochondrial ROS production, which in turn induces mitochondrial dysfunction in MDA-MB-231 cells. NMac1 inhibits Complex I activity and suppresses changes in morphology and actin cytoskeleton organization following Rac1 activation in MDA-MB-231 cells. NMac1 inhibits tumor invasion, migration and metastasis. NMac1 is useful for studying metastatic tumors, such as breast cancer. NMac1 can be isolated from the ginger cassumunar Roxb^[1][2]. In Vitro:NMac1 inhibits the proliferation of cancer cells under glucose starvation (IC₅₀s of 7.197 and 2.849 μM) in MDA-MB-231 and MCF7 cells^[1].
NMac1 (0-20 μM, 0-20 h) induces AMPK activation and inhibits mTOR and ERK in the absence of glucose in MDA-MB-231 cells^[1].
NMac1 (0-20 μM, 0-20 h) induces mitochondrial dysfunction by inhibiting ATP production and reducing the mitochondrial membrane potential in MDA-MB-231 cells^[1].
NMac1 (0-10 μM, 0-100 min) induces ATP depletion by reducing oxygen consumption rate, producing mitochondrial ROS and inducing dysregulation of mitochondrial ATP production system OXPHOS in the absence of glucose in MDA-MB-231 cells^[1].
NMac1 (250-500 μM, 0-100 min) inhibits complex I activity in MDA-MB-231 cells^[1].
NMac1 (0-30 μM, 2-14 days) inhibits the proliferation of MDA-MB-231 spheroid cells in a dose-dependent manner^[1].
NMac1 (0-25 μM, 16-24 h) inhibits Rac1 activation through NDPK activation of Nm23-H1, reduces the invasion and migration in MDA-MB-231 cells^[2].
In Vivo:NMac1 (10 mg/kg, p.o., once a day, 21 days) inhibits breast cancer metastasis without affecting primary tumor size in breast cancer metastasis mouse model^[2].