RAF709 Chemical Properties

Boiling point:

622.7±55.0 °C(Predicted)

Density 

1.321±0.06 g/cm3(Predicted)

storage temp. 

Store at -20°C

solubility 

DMSO:100.0(Max Conc. mg/mL);184.31(Max Conc. mM)
DMSO:PBS (pH 7.2) (1:2):0.33(Max Conc. mg/mL);0.61(Max Conc. mM)
DMF:30.0(Max Conc. mg/mL);55.29(Max Conc. mM)
Ethanol:100.0(Max Conc. mg/mL);184.31(Max Conc. mM)

form 

A crystalline solid

pka

11.87±0.70(Predicted)

color 

White to off-white

Safety Information

HS Code 

2934999090

RAF709 Usage And Synthesis

Description

RAF709 is a potent inhibitor of B-RAF and C-RAF (IC₅₀s = 0.4 and 0.5 nM, respectively). It is selective for RAF kinases exhibiting >99% inhibition of only B-RAF, B-RAF^V600E, and C-RAF in a panel of 456 kinases. However, DDR1, DDR2, FRK, and PDGFRβ are also inhibited by >80% at a concentration of 1 μM. RAF709 inhibits phosphorylation of MEK and ERK (EC₅₀s = 0.02 and 0.1 μM, respectively) with minimal paradoxical activation, stabilizes BRAF-CRAF dimers (EC₅₀ = 0.8 μM), and reduces proliferation of Calu-6 RAS mutant cells (EC₅₀ = 0.95 μM). In a Calu-6 mouse non-small cell lung cancer (NSCLC) xenograft model, RAF709 (10-200 mg/kg) reduces ERK phosphorylation and decreases tumor volume in a dose-dependent manner without affecting total body weight.

Uses

RAF709 is a potent, selective, and efficacious RAF inhibitor with IC50s of 0.4 nM and 0.5 nM for BRAF and CRAF, respectively[1]. Antitumor efficacy[1].

in vivo

IC 50

CRAF: 0.5 nM (IC₅₀); Braf: 0.4 nM (IC₅₀)

References

[1] Nishiguchi GA, et al. Design and Discovery of N-(2-Methyl-5'-morpholino-6'-((tetrahydro-2H-pyran-4-yl)oxy)-[3,3'-bipyridin]-5-yl)-3-(trifluoromethyl)benzamide (RAF709): A Potent, Selective, and Efficacious RAF Inhibitor Targeting RAS Mutant Cancers. J Med Chem. 2017 Jun 22;60(12):4869-4881. DOI:10.1021/acs.jmedchem.6b01862

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