NSC 95397 (Synonyms: Cdc25 Inhibitor IV, PTP Inhibitor XXIX)

NSC 95397 is a potent, selective Cdc25 dual specificity phosphatase inhibitor (Ki=32 nM (Cdc25A), 96 nM (Cdc25B), 40 nM (Cdc25C); IC50=22.3 nM (human Cdc25A), 56.9 nM (human Cdc25C), 125 nM (Cdc25B))[1]. NSC 95397 inhibits mitogen-activated protein kinase phosphatase-1 (MKP-1) and suppresses proliferation and induces apoptosis in colon cancer cells through MKP-1 and ERK1/2 pathway[2].

NSC 95397 (0, 10, and 20 µM; 24 hour) decreases the cell viability of three colon cancer cell lines SW480, SW620, and DLD-1 in a concentration-dependent manner[2].NSC 95397(10 μM; 24 hour) upregulates p21 while downregulates CDK4 and CDK6 were d in all three colon cancer cell lines SW480, SW620, and DLD-1 cells[2]. NSC 95397 (10 μM; 24 hour) reduces the phosphorylation of retinoblastoma protein (Rb) on Ser795 and Ser807/811[2]. NSC 95397 (20 μM; 24 hours) significantly increases cleaved caspase-9, -3, -7 and PARP levels[2]. NSC 95397 (10 μM; 6 hours) enhances the phosphorylation of its downstream ERK1/2 at Thr202/Tyr 204[2].

References:
[1]. Lazo JS, et al. Identification of a potent and selective pharmacophore for Cdc25 dual specificity phosphatase inhibitors. Mol Pharmacol. 2002 Apr;61(4):720-8.
[2]. Dubey NK, et al. NSC 95397 Suppresses Proliferation and Induces Apoptosis in Colon Cancer Cells through MKP-1 and the ERK1/2 Pathway. Int J Mol Sci. 2018 May 31;19(6). pii: E1625.