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Details

Stereochemistry ACHIRAL
Molecular Formula C24H16F6N6O
Molecular Weight 518.4139
Optical Activity UNSPECIFIED
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=CC(OC4=CC(=NC=C4)C5=NC=C(N5)C(F)(F)F)=CC=C13

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

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

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

PubMed

PubMed

TitleDatePubMed
Dependence on phosphoinositide 3-kinase and RAS-RAF pathways drive the activity of RAF265, a novel RAF/VEGFR2 inhibitor, and RAD001 (Everolimus) in combination.
2010 Feb
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.
2010 Nov 24
Comprehensive analysis of kinase inhibitor selectivity.
2011 Oct 30
Patents

Sample Use Guides

In Vivo Use Guide
MTD was 48 mg once daily
Route of Administration: Oral
Substance Class Chemical
Created
by admin
on Tue Oct 22 12:36:59 UTC 2019
Edited
by admin
on Tue Oct 22 12:36:59 UTC 2019
Record UNII
8O434L3768
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
RAF-265
Common Name English
1-METHYL-5-((2-(5-(TRIFLUOROMETHYL)-1H-IMIDAZOL-2-YL)-4-PYRIDINYL)OXY)-N-(4-(TRIFLUOROMETHYL)PHENYL)-1H-BENZIMIDAZOL-2-AMINE
Systematic Name English
NVP-RAF265
Code English
RAF265
Code English
CHIR-265
Code English
RAF 265 [WHO-DD]
Common Name English
Code System Code Type Description
ChEMBL
CHEMBL558752
Created by admin on Tue Oct 22 12:36:59 UTC 2019 , Edited by admin on Tue Oct 22 12:36:59 UTC 2019
PRIMARY
PUBCHEM
11656518
Created by admin on Tue Oct 22 12:36:59 UTC 2019 , Edited by admin on Tue Oct 22 12:36:59 UTC 2019
PRIMARY
CAS
927880-90-8
Created by admin on Tue Oct 22 12:36:59 UTC 2019 , Edited by admin on Tue Oct 22 12:36:59 UTC 2019
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
Related Record Type Details
ACTIVE MOIETY