Ilorasertib

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

Ilorasertib (ABT-348) 是一种 ATP 竞争性多靶点激酶抑制剂，可抑制 Aurora A/Aurora B/Aurora C (IC50: 120 nM/7 nM/1 nM)。

Ilorasertib (ABT-348) is an ATP-competitive multitargeted kinase inhibitor, which inhibits Aurora A/Aurora B/Aurora C (IC50s: 120 nM/7 nM/1 nM). It also suppresses RET tyrosine kinase, PDGFRβ, and Flt1 (IC50s: 7 nM, 3 nM, and 32 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 (EC50: 5, 10 nM). Ilorasertib shows antiproliferative activity against BCR-ABL expressing CML cells and cells expressing the Gleevec-resistant BCR-ABL T315I mutation (IC50: 47, 260 nM).Ilorasertib inhibits the VEGF response with a potency (ED50: 0.2 mg/kg, i.v.) in a uterine edema model. 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 (20 mg/kg, p.o.) inhibits the growth of established tumors and causes regression of advanced tumors in human xenograft models. Ilorasertib demonstrates significant antitumor efficacy in both solid and hematological xenograft models after intravenous, mini-pump or parenteral once-weekly dosing.

Ilorasertib (0, 3, 10, 30 nM; 24 h) induces a concentration-dependent increase in the extent and number of H1299, H460 cells.Ilorasertib (1-1000 nM) shows antiproliferative activity. Cell Viability Assay Cell 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 EC50S of 5, 10 nM for H1299, H460 cells, respectively.Cell Proliferation Assay Cell Line:MV-4-11, SEM, K562, HCT-15, SW620, H1299, H460 cells Concentration:1-1000 nM Incubation Time:Result:Showed antiproliferative activity with IC50s of 0.3, 1, 103, 6, 6, 2, 2 nM for MV-4-11, SEM, K562, HCT-15, SW620, H1299, H460 cells, respectively.

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.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.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.Ilorasertib (0.2 mg/kg; i.v.) shows anti-VEGF activity in mouse.Ilorasertib (20 mg/kg; p.o.;once weekly for 3 weeks) shows anti-tumor activity in mouse. Animal Model:Female SCID/beige mice Dosage: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.

ABT-348

Cell Cycle/DNA Damage

Aurora Kinase

Aurora A| Aurora B| Aurora C| PDGFRβ| RET| FLT1| VEGFR1| VEGFR2| VEGFR3

Cancer

Solid tumours

1227939-82-3

488.54

C25H21FN6O2S

>98% (HPLC)

DMSO:40 mg/mL (81.87 mM; Need ultrasonic)

Nc1ncc(-c2cnn(CCO)c2)c2scc(-c3ccc(NC(=O)Nc4cccc(F)c4)cc3)c12

——

(-20℃)

With Ice Pack

≥ 2 years