MBM-17S

MBM-17S is a potent NIMA-related kinase 2 (Nek2) inhibitor, with an IC50 of 3 nM. MBM-17S effectively inhibits the proliferation of cancer cells by inducing cell cycle arrest and apoptosis. MBM-17S shows antitumor activities, and no obvious toxicity to mice[1].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

IC50: 3 nM (Nek2), 5800 nM (Aurora A)[1]

MBM-17S inhibits MGC-803, HCT-116, and Bel-7402 cells proliferation with IC50s of 0.48, 1.06, and 4.53 μM, respectively[1]. MBM-17S (0.25-1.0 μM; 24 hours) induced G2/M phase arrest and accumulation of cells with >4N content[1]. MBM-17S (0.5-1.0 μM; 24 hours) triggers apoptosis of cancer cells[1]. Cell Cycle Analysis[1] Cell Line: HCT-116 and MGC-803 cells Concentration: 0.25-1.0 μM Incubation Time: 24 hours Result: Obvious accumulation of cells in the G2/M phase with >4 N DNA content. Apoptosis Analysis[1] Cell Line: HCT-116 and MGC-803 cells Concentration: 0.5 μM, 1.0 μM Incubation Time: 24 hours Result: For HCT-116 cells, the percentage of total apoptotic cells was 39.3%±3.8% and 47.1%±0.6% at 0.5 μM and 1.0 μM, respectively. For MGC-803 cells, the percentage of total apoptotic cells increased to 32.9%±4.6% and 41.1%±0.2% at 0.25 μM and 0.5 μM, respectively.

MBM-17S (20 mg/kg; i.p.; twice a day for 21 days) exhibits good antitumor activity and a well-tolerated dose schedule[1]. MBM-17S (1.0 mg/kg; i.v.) treatment shows CL, Vss, T1/2, AUC0-t, and AUC0-∞ values of 42.4 mL/min/kg, 4.06 L/kg, 2.42 hours, 386 ng/h/mL, and 405 ng/h/mL, respectively[1]. Animal Model: Female BALB/c nu/nu mice (5-6 weeks, bearing HCT-116 xenografts)[1] Dosage: 20 mg/kg Administration: Intraperitoneal injection; twice a day for 21 days Result: Tmor growth was significantly suppressed. Animal Model: Male Sprague Dawley (SD) rats[1] Dosage: 1.0 mg/kg Administration: IV injection (Pharmacokinetic Analysis) Result: The CL, Vss, T1/2, AUC0-t, and AUC0-∞ values of 42.4 mL/min/kg, 4.06 L/kg, 2.42 hours, 386 ng/h/mL, and 405 ng/h/mL, respectively.

[1]. Xi JB, et al. Structure-based design and synthesis of imidazo[1,2-a]pyridine derivatives as novel and potent Nek2 inhibitors with in vitro and in vivo antitumor activities. Eur J Med Chem. 2017 Jan 27;126:1083-1106.