RAF709

Cas：1628838-42-5

Product Information：

RAF709 is a Raf kinase inhibitor.

Chemical Formula: C28H29F3N4O4

Exact Mass: 542.2141

Molecular Weight: 542.5592

Elemental Analysis: C, 61.99; H, 5.39; F, 10.50; N, 10.33; O, 11.80

Synonym: 

RAF709

RAF-709

RAF 709

Chemical Name: N-(2-methyl-5'-morpholino-6'-((tetrahydro-2H-pyran-4-yl)oxy)-[3,3'-bipyridin]-5-yl)-3-(trifluoromethyl)benzamide

InChi Key: 

FYNMINFUAIDIFL-UHFFFAOYSA-N

InChi Code: InChI=1S/C28H29F3N4O4/c1-18-24(15-22(17-32-18)34-26(36)19-3-2-4-21(13-19)28(29,30)31)20-14-25(35-7-11-38-12-8-35)27(33-16-20)39-23-5-9-37-10-6-23/h2-4,13-17,23H,5-12H2,1H3,(H,34,36)

Smiles Code:

O=C(NC1=CN=C(C)C(C2=CC(N3CCOCC3)=C(OC4CCOCC4)N=C2)=C1)C5=CC(C(F)(F)F)=CC=C5

Technical Data：

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

In Vitro:

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.

In Vivo:

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.

References：

1. Maxson JE, Abel ML, Wang J, Deng X, Reckel S, Luty SB, Sun H, Gorenstein J, Hughes SB, Bottomly D, Wilmot B, McWeeney SK, Radich J, Hantschel O, Middleton RE, Gray NS, Druker BJ, Tyner JW. Identification and Characterization of Tyrosine Kinase Nonreceptor 2 Mutations in Leukemia through Integration of Kinase Inhibitor Screening and Genomic Analysis. Cancer Res. 2016 Jan 1;76(1):127-38. doi: 10.1158/0008-5472.CAN-15-0817. PubMed PMID: 26677978; PubMed Central PMCID: PMC4703549.

Products are for research use only. Not for human use.