SW106065

SW106065 is an apoptosis inducer in malignant peripheral nerve sheath tumors (MPNST). SW106065 inhibits ATP consumption of sMPNST and other models of MPNST with an EC50 of 1 µM. SW106065 can be used for MPNST research[1].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

SW106065 (Compound 21, Cpd21) inhibits the human MPNST cell lines growth in a dose-dependent manner, and EC50 concentrations of 439 nM and 753.6 nM for S462 and SNF96.2 cells, respectively. SW106065 remains nontoxic to normally dividing Schwann cells or mouse embryonic fibroblasts[1]. SW106065 (Cpd21; 0.25-5 µM; 24 hours; sMPNST cells) treatment shows a decreased percentage of cells in S phase, and a corresponding increased percentage in G1/G0 and G2/M[1]. SW106065 (Cpd21; 0.25-5 µM; 24 hours; sMPNST cells) treatment decreases the levels of cyclin A2, cyclin B1, cyclin D1, cyclin E, cdk4, and cdk6. And increases levels of cdkn1a and cdkn2a mRNA were observed in a dose-dependent manner.SW106065 (Cpd21; 0.25-5 µM; 24 hours; sMPNST cells) treatment decreases the levels of Cyclin D1 protein[1]. SW106065 (Cpd21) treatment significant increase in the percentage of apoptotic cells[1]. Cell Cycle Analysis[1] Cell Line: sMPNST cells Concentration: 0.25 µM, 0.5 µM, 1 µM, 2.5 µM, and 5 µM Incubation Time: 24 hours Result: Showed a decreased percentage of cells in S phase, and a corresponding increased percentage in G1/G0 and G2/M. RT-PCR[1] Cell Line: sMPNST cells Concentration: 0.25 µM, 0.5 µM, 1 µM, 2.5 µM, and 5 µM Incubation Time: 24 hours Result: Decreased levels of cyclin A2, cyclin B1, cyclin D1, cyclin E, cdk4, and cdk6. Increased levels of cdkn1a and cdkn2a mRNA were observed in a dose-dependent manner. Western Blot Analysis[1] Cell Line: sMPNST cells Concentration: 0.25 µM, 0.5 µM, 1 µM, 2.5 µM, and 5 µM Incubation Time: 24 hours Result: Decreased levels of Cyclin D1 protein.

SW106065 (Cpd21; 40 mg/kg; intraperitoneal injection; twice per day for 4 weeks) treatment can be delivered to mice in concentrations to sufficiently penetrate sMPNST tissue, and inhibit tumor development[1]. Animal Model: NCR-nu/nu female mice (6-7 week old) injected with MPNST cells[1] Dosage: 40 mg/kg Administration: Intraperitoneal injection; twice per day for 4 weeks Result: Reduced MPNST burden in a mouse allograft model.

[1]. Vincent Chau, et al. Preclinical therapeutic efficacy of a novel pharmacologic inducer of apoptosis in malignant peripheral nerve sheath tumors. Cancer Res. 2014 Jan 15;74(2):586-97.