RAF-709

SKU: orb1226021

Description

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.

Key Properties

• CAS Number: 1628838-42-5
• MW: 542.5495
• Purity: >98% (HPLC)
• Formula: C₂₈H₂₉F₃N₄O₄
• SMILES: CC1=C(C=C(C=N1)NC(=O)C2=CC(=CC=C2)C(F)(F)F)C3=CC(=C(N=C3)OC4CCOCC4)N5CCOCC5
• Target: Raf
• Solubility: DMSO: 100 mg/mL

Bioactivity

• 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.
• 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.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

RAF709 | RAF 709

Quick Database Links

Gene Symbol

Raf