Ilorasertib

Ilorasertib (ABT-348) is a potent, orally active and ATP-competitive aurora inhibitor with IC₅₀s of116, 5, 1 nM for aurora A, aurora B, aurora C, respectively. Ilorasertib also is a potent VEGF, PDGF inhibitor. Ilorasertib has the potential for the research of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)^[1][2]. IC50 & Target: IC50: 7 nM (RET)^[1], 1 nM (Aurora C), 7 nM (Aurora B), 120 nM (Aurora A), 12 nM (Aurora B^Y156H), 11 nM (PDGFRα), 13 nM (PDGFRβ), 1 nM (VEGFR1), 2 nM (VEGFR2), 43 nM (VEGFR3), 1 nM (FLT3), 3 nM (CSF-1R), 20 nM (c-KIT)^[2] In Vitro: Ilorasertib (0, 3, 10, 30 nM; 24 h) induces a concentration-dependent increase in the extent and number of H1299, H460 cells^[2].
Ilorasertib (1-1000 nM) shows antiproliferative activity^[2]. In Vivo: Ilorasertib (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^[1].
Ilorasertib (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^[1].
Ilorasertib (0, 3.75, 7.5, 15 mg/kg; i.p.) inhibits the histone H3 phosphorylation at 4-8 h in blood-borne tumor cells^[2].
Ilorasertib (0.2 mg/kg; i.v.) shows anti-VEGF activity in mouse^[2].
Ilorasertib (20 mg/kg; p.o.;once weekly for 3 weeks) shows anti-tumor activity in mouse^[2].