Ilorasertib hydrochloride (C09-1140-526)

Ilorasertib (ABT-348) hydrochloride is a potent, orally active and ATP-competitive aurora inhibitor with IC 50 s of116, 5, 1 nM for aurora A , aurora B , aurora C , respectively. Ilorasertib hydrochloride also is a potent VEGF , PDGF inhibitor. Ilorasertib hydrochloride has the potential for the research of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).In VitroIlorasertib hydrochloride (0, 3, 10, 30 nM; 24 h) induces a concentration-dependent increase in the extent and number of H1299, H460 cells. Ilorasertib hydrochloride (1-1000 nM) shows antiproliferative activity. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Viability AssayCell Line: H1299, H460 cells Concentration: 0, 3, 10, 30 nM Incubation Time: 24 h Result: Induced a concentration-dependent increase in the extent and number of cells exhibiting polyploidy with EC 50 S of 5, 10 nM for H1299, H460 cells, respectively. Cell Proliferation AssayCell Line: MV-4-11, SEM, K562, HCT-15, SW620, H1299, H460 cells Concentration: 1-1000 nM Incubation Time: Result: Showed antiproliferative activity with IC 50 s of 0.3, 1, 103, 6, 6, 2, 2 nM for MV-4-11, SEM, K562, HCT-15, SW620, H1299, H460 cells, respectively.In VivoIlorasertib hydrochloride (6.25, 12.5, 25 mg/kg; p.o.) shows anti-tumor activity in MV-4-11 tumor-bearing SCID mice with TGI of 80%, 86%, 94% at 6.25, 12.5, 25 mg/kg, respectively . Ilorasertib hydrochloride (6.25, 12.5, 25 mg/kg; p.o.) shows anti-tumor activity in SKM-1 tumor-bearing SCID mice with TGI of 38%, 59%, 80% at 6.25, 12.5, 25 mg/kg, respectively . Ilorasertib hydrochloride (0, 3.75, 7.5, 15 mg/kg; i.p.) inhibits the histone H3 phosphorylation at 4-8 h in blood-borne tumor cells. Ilorasertib hydrochloride (0.2 mg/kg; i.v.) shows anti-VEGF activity in mouse. Ilorasertib hydrochloride (20 mg/kg; p.o.;once weekly for 3 weeks) shows anti-tumor activity in mouse. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Female SCID/beige miceDosage: 25 mg/kg Administration: Subcutaneous minipump; 24 h Result: Inhibited the histone H3 phosphorylation and the tumor drug concentration associated with 50% inhibition of histone H3 phosphorylation. Animal Model: 22-26 g, female NOD/SCID mice (xenograft model of multiple myeloma (KMS11))Dosage: 20 mg/kg Administration: P.o.; once weekly for 3 weeks Result: Inhibited the tumor growth in mouse. Specification: 10mM in DMSO Molecular Formula: C25H22ClFN6O2S Molecular Weight: 525