RAF-709

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

一种新型有效、选择性、口服生物可利用的 RAF 抑制剂，对 BRAF 和 CRAF 的生化 IC50 分别为 0.4 nM 和 0.5 nM。

A novel potent, selective, and orally bioavailable RAF inhibitor with biochemical IC50 of 0.4 nM and 0.5 nM for BRAF and CRAF, respectively; suppresses pERK (EC50=0.02-0.1 uM), stabilizes BRAF?CRAF dimers(EC50=0.8 uM) inhibits proliferation (EC50=0.95 uM) in KRAS mutant tumor cell lines (Calu6); shows effectivity in a KRAS mutant xenograft model.

RAF709 stabilizes BRAF-CRAF dimers with an EC50 of 0.8 μM. In cellular assays, the dose-response of pMEK and pERK are measured in Calu-6 cells with EC50=0.02 and 0.1 μM with minimal paradoxical activation and inhibition of proliferation with EC50=0.95 μM.

RAF709 proves to be soluble, kinase selective, and efficacious in a KRAS mutant xenograft model. RAF709 shows dose-proportional increases in plasma exposure and a corresponding dosedependent inhibition of pERK in Calu-6 tumors. Treatment with RAF709 results in dose-dependent antitumor activity with 10 mg/kg being subefficacious (%T/C=92%), 30 mg/kg results in measurable antitumor activity (%T/C=46%), and 200 mg/kg results in mean tumor regression of 92%, while the same high dose is not efficacious in the PC3, KRAS WT model.

RAF709 | RAF 709

MAPK/ERK Signaling

Raf

B-Raf|C-Raf

Cancer

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1628838-42-5

542.5495

C28H29F3N4O4

>98% (HPLC)

DMSO: 100 mg/mL

CC1=C(C=C(C=N1)NC(=O)C2=CC(=CC=C2)C(F)(F)F)C3=CC(=C(N=C3)OC4CCOCC4)N5CCOCC5

Benzamide, N-[2-methyl-5'-(4-morpholinyl)-6'-[(tetrahydro-2H-pyran-4-yl)oxy][3,3'-bipyridin]-5-yl]-3-(trifluoromethyl)-

(-20℃)

With Ice Pack

≥ 2 years