R1530

Research use only, not for human use.

R1530 is a multikinase inhibitor with antineoplastic and antiangiogenesis activities.

R1530 is a multikinase inhibitor with antineoplastic and antiangiogenesis activities.(In Vitro):R1530 inhibits multiple receptor tyrosine kinases involved in angiogenesis, such as VEGFR-1/2/3, PDGFR, Flt-3 and FGFR-1/2. R1530 enables polyploid cancer cells to undergo apoptosis or senescence, which translates into potent in vitro and in vivo efficacy. Normal proliferating cells are resistant to R1530-induced polyploidy. The mitotic checkpoint kinase BubR1 is downregulated during R1530-induced mitotic exit, possibly as a result of PLK4 inhibition. R1530 strongly inhibits human tumor cell proliferation. Growth factor-driven endothelial and fibroblast proliferation is also inhibited.(In Vivo):Showing significant tumor growth inhibition in a lung cancer xenograft model, R1530 was administered at doses ranging from once daily, weekly and twice weekly (3.125-50 mg/kg qd, 100 mg/kg qw, 100 mg/kg kg biw). Tumor regression occurred in all models treated with the maximum tolerated daily dose (50 mg/kg). Doses of 25 and 50 mg/kg qd resulted in biologically significant increases in survival in all models tested. After oral administration to nude mice, R1530 showed good tissue permeability. Exposure was dose-dependent, up to 100 mg/kg when administered orally.

R1530 exhibits potent in vitro antiproliferative activity in all of the tumor cell lines ( IC50 = 0.2?3.4 μM). R1530 inhibits the kinase activities of vascular endothelial growth factor receptor 2 (VGFr2), FGFr1 and PDGFr-β. R1530 has inhibition of VEGF and bFGF induces HUVEC proliferation ( IC50 = 49 and 118 nM).

R1530 (1.56, 25, and 50 mg/kg; p.o.; daily, for 28 days.) has notable antitumor activity across a broad range of human xenograft models, with minimal toxicity. Animal Model:Human tumor xenograft models Dosage:1.56, 25 and 50 mg/kg Administration:Oral administration; daily, for 28 days. Result:Inhibited tumor growth in all models, with regression observed in all models tested at a 50 mg/kg dose.

R 1530 | R-1530

Angiogenesis

VEGFR

VEGFR

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882531-87-5

356.79

C18H14ClFN4O

>98% (HPLC)

In Vitro:?DMSO : 50 mg/mL (140.14 mM)

COc1cc2N=C3NNC(C)=C3N=C(c3ccccc3Cl)c2cc1F

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(-20℃)

With Ice Pack

≥ 2 years