ZMF-10

ZMF-10 is a highly potent PAK1 inhibitor, with IC50s of 174 nM, 1.038 μM and 1.372 μM for PAK1, PAK2 and PAK3, respectively. ZMF-10 can inhibit PAK1 activity to affect PAK1-regulated apoptosis, ER-Stress and migration in MDA-MB-231 cells. ZMF-10 can be used for researching anticancer[1].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Cytoskeleton >> PAK

Signaling Pathways >> Cell Cycle/DNA Damage >> PAK

PAK1:174 nM (IC50)

PAK2:1.038 μM (IC50)

PAK3:1.372 μM (IC50)

ZMF-10 (0-10 μM; 48 hours) exhibits potent antiproliferative activity in a dose-dependent manner[1]. ZMF-10 (20 μM; 24 hours) suppresses the phosphorylation of PAK1 at Ser199 and Thr212[1]. ZMF-10 (10-40 μM; 24 hours) downregulates the expression of ERK, and suppresses the phosphorylation of c-Raf, MEK and ERK; up-regulates the expression of Bax and downregulates the expression of Bcl-2; induces apoptosis in a dose-dependent manner with the increase of early and late apoptotic cell population[1]. ZMF-10 (10-40 μM; 24 hours) inhibits the PI3K-AKT-mTOR signaling with the decreasing phosphorylation of AKT and mTOR; inhibits JNK1/2 and cells migration in MDA-MB-231 cells[1]. Cell Proliferation Assay Cell Line: MDA-MB-231[1] Concentration: 0-10 μM Incubation Time: 48 hours Result: Exhibited potent antiproliferative activity in a dose-dependent manner with an IC50 value of 3.48 μM. Immunofluorescence Cell Line: MDA-MB-231[1] Concentration: 20 μM Incubation Time: 24 hours Result: Suppressed the phosphorylation of PAK1 at Ser199 and Thr212. Western Blot Analysis Cell Line: MDA-MB-231[1] Concentration: 10, 20 and 40 μM Incubation Time: 24 hours Result: Downregulated the expression of ERK, and suppressed the phosphorylation of c-Raf, MEK and ERK; up-regulated the expression of Bax and downregulated the expression of Bcl-2. Apoptosis Analysis Cell Line: MDA-MB-231[1] Concentration: 10, 20 and 40 μM Incubation Time: 24 hours Result: Induced apoptosis in a dose-dependent manner with the increase of early and late apoptotic cell population.

[1]. Zhang J, et al. Design, synthesis and biological evaluation of 1H-pyrazolo [3,4-d]pyrimidine derivatives as PAK1 inhibitors that trigger apoptosis, ER stress and anti-migration effect in MDA-MB-231 cells. Eur J Med Chem. 2020;194:112220.