MBM-55S

MBM-55S is a potent NIMA-related kinase 2 (Nek2) inhibitor with an IC50 of 1 nM. MBM-55S shows a 20-fold or greater selectivity in most kinases with the exception of RSK1 (IC50=5.4 nM) and DYRK1a (IC50=6.5 nM). MBM-55S effectively inhibits the proliferation of cancer cells by inducing cell cycle arrest and apoptosis. MBM-55S shows antitumor activities, and no obvious toxicity to mice[1].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> DYRK

Signaling Pathways >> MAPK/ERK Pathway >> Ribosomal S6 Kinase (RSK)

IC50: 1 nM (Nek2), 5.4 nM (RSK1), 6.5 nM (DYRK1a), 57 nM (CHK1), 91 nM (GSK-3β), 20 nM (ABL), 370 nM (CDK2), 441nM (CDK4), 608 nM (AKT1), 5300 nM (Aurora A)[1]

MBM-55S inhibits MGC-803, HCT-116, Bel-7402 cells proliferation with IC50s of 0.53, 0.84, 7.13 μM, respectively[1]. MBM-55S (0.5-1 μM; 24 hours) induces G2/M phase arrest and accumulation of cells with >4N content in HCT-116 cells[1]. MBM-55S (0.5-1 μM; 24 hours) causes cell apoptosis in a concentration-dependent manner in HCT-116 cells[1]. Cell Cycle Analysis[1] Cell Line: HCT-116 cells Concentration: 0.5, 1 μM Incubation Time: 24 hours Result: Induced G2/M phase arrest and accumulation of cells with >4N content. Apoptosis Analysis[1] Cell Line: HCT-116 cells Concentration: 0.5, 1 μM Incubation Time: 24 hours Result: Caused cell apoptosis in a concentration-dependent manner.

MBM-55S (20 mg/kg; i.p.; twice a day for 21 days) exhibits good antitumor activity and a well-tolerated dose schedule in nude mice bearing HCT-116 xenografts[1].MBM-55S (1.0 mg/kg; i.v.) treatment shows the CL, Vss, T1/2, AUC0-t, and AUC0-∞ values of 33.3 mL/min/kg, 2.53 L/kg, 1.72 hours, 495 ng/h/mL and 507 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: Significantly suppressed tumor growth. 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 were 33.3 mL/min/kg, 2.53 L/kg, 1.72 hours, 495 ng/h/mL and 507 ml/min/kg, 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.