tcsc6804 Ilorasertib

Ilorasertib (ABT-348) is an ATP-competitive multitargeted kinase inhibitor with IC₅₀s for inhibiting binding Aurora B (7 nM), C (1 nM), and A (120 nM), and also inhibits RET tyrosine kinase, PDGFRβ, and Flt1 with IC₅₀s of 7 nM, 3 nM and 32 nM.

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 is an ATP-competitive multitargeted kinase inhibitor with IC₅₀ for inhibiting cellular autophosphorylation of Aurora B (13 nM), C (13 nM), and A (189 nM). In addition to targeting Aurora kinases, Ilorasertib is a potent inhibitor of the VEGFR and PDGFR kinase families and, to a lesser extent, the Src family of cytoplasmic tyrosine kinases. Ilorasertib induces a concentration-dependent increase in the extent and number of two NSCLC cell lines exhibiting polyploidy. The potency for inducing this response (EC₅₀ = 5 and 10 nM). Ilorasertib shows antiproliferative activity against BCR-ABL expressing CML cells and cells expressing the gleevec-resistant BCR-ABL T315I mutation (IC₅₀ = 47 and 260 nM)^[2].

In Vivo: Ilorasertib (25 mg/kg, s.c.) leads to an inhibition of histone H3 phosphorylation in circulating tumor cells obtained from an engrafted leukemia model. Ilorasertib inhibits the VEGF response with a potency (ED₅₀ = 0.2 mg/kg i.v.) in a uterine edema model. Ilorasertib (20 mg/kg, p.o.) inhibits the growth of established tumors and causes regression of advanced tumors in human xenograft models^[2]. Ilorasertib demonstrates significant antitumor efficacy in both solid and hematological xenograft models after intravenous, mini-pump or parenteral once-weekly dosing^[3].