U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C24H16F6N6O
Molecular Weight 518.4139
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of RAF-265

SMILES

CN1C(NC2=CC=C(C=C2)C(F)(F)F)=NC3=C1C=CC(OC4=CC=NC(=C4)C5=NC=C(N5)C(F)(F)F)=C3

InChI

InChIKey=YABJJWZLRMPFSI-UHFFFAOYSA-N
InChI=1S/C24H16F6N6O/c1-36-19-7-6-15(10-17(19)34-22(36)33-14-4-2-13(3-5-14)23(25,26)27)37-16-8-9-31-18(11-16)21-32-12-20(35-21)24(28,29)30/h2-12H,1H3,(H,32,35)(H,33,34)

HIDE SMILES / InChI

Description

CHIR-265 (RAF265) is a potent selective orally active small molecule Raf-kinase inhibitor with anti‐angiogenic activity through inhibition of vascular endothelial growth factor type 2 (VEGFR‐2) in preclinical models. CHIR-265 effectively block phosphorylation of Raf's downstream substrates MEK and ERK in cells and also kill melanoma and colorectal cancer cell lines harboring B-Raf mutations independent of PTEN mutation status. Raf kinase inhibition by CHIR-265 in mutant B-Raf melanoma cell lines causes cell cycle arrest and induces apoptosis, mimicking the effect of Raf RNAi in these cells. CHIR-265 also potently inhibits the phosphorylation of VEGFR2 and proliferation of VEGF-stimulated hMVEC.

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
20.0 nM [IC50]
20.0 nM [IC50]
20.0 nM [IC50]
6.0 nM [IC50]

PubMed

Sample Use Guides

In Vivo Use Guide
MTD was 48 mg once daily
Route of Administration: Oral