Onvansertib

NMS-1286937 is a potent, selective and orally available PLK1 inhibitor, with an IC₅₀ of 2 nM. IC50 & Target: IC50: 2 nM (PLK1)^[1] In Vitro: NMS-1286937 is a potent, selective and orally available PLK1 inhibitor, with IC₅₀ of 2 nM. NMS-1286937 also shows inhibitory activities against FLT3, MELK, and CK2, with IC₅₀s of 510, 744, and 826 nM, respectively^[1]. NMS-P937 possesses a pure ATP competitive mechanism with a reversible dissociation and no time dependency. NMS-P937 (10 μM) is selective with a marginal activity of 48% and 40% inhibition on PLK2 and PLK3, respectively. NMS-P937 shows antiproliferative activity against a panel of 137 cell lines, with IC₅₀ values of below 100 nM for 60 of 137 cell lines and higher than 1 μM for only 9 of 137 cell lines^[2]. NMS-P937 shows cytotoxic activity against AmL-NS8 cells with IC₅₀ of 36 nM^[3]. In Vivo: NMS-1286937 (45 mg/kg, i.v.) shows a good tumor growth inhibition with acceptable and reversible body weight loss in CD1 nu/nu mice xenografted with human HCT116 colon adenocarcinoma cells. NMS-1286937 (60 mg/kg, p.o.) also inhibits the growth of tumor on HCT116 xenograft model^[1]. NMS-P937 (45 mg/kg, i.v.or 60 mg/kg, p.o) inhibits tumor growth to a comparable degree (TGI, 83% and 79% intravenously and orally, respectively) in HCT116-bearing mice. The combination of NMS-P937 (120 mg/kg given for 4 cycles of 2 consecutive days with 10-day rest) and cytarabine (75 mg/kg for 4 cycles of 5 consecutive days with 7-day rest) in the disseminated leukemia model AmL-PS is well tolerated and clearly showed increased mice survival^[2]. NMS-P937 (60 mg/kg bid os per day over 2 days with a 5 day rest) shows good efficacy compared to standard therapies, with a significant increase in median survival time (MST) in the established disease setting^[3].