RAF-265

Investigational

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 Search

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	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23617957 | https://www.ncbi.nlm.nih.gov/pubmed/28719152 | https://www.ncbi.nlm.nih.gov/pubmed/26396681 | https://www.ncbi.nlm.nih.gov/pubmed/26081844

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 Target	Pharmacology	Potency
Serine/threonine-protein kinase B-raf 21 Target ID: CHEMBL5145 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26396681	Inhibitor 8504	20.0 nM [IC50]
Vascular endothelial growth factor receptor 11 Target ID: CHEMBL2095227 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26396681	Inhibitor 8504	20.0 nM [IC50]
Mast/stem cell growth factor receptor Kit 6 Target ID: P10721 Gene ID: 3815.0 Gene Symbol: KIT Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/26396681	Inhibitor 8504	20.0 nM [IC50]
Platelet-derived growth factor receptor beta 56 Target ID: P09619 Gene ID: 5159.0 Gene Symbol: PDGFRB Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/26396681	Inhibitor 8504	6.0 nM [IC50]

C_max

Value	Dose	Analyte	Population
0.14 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719152/	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	CHIR-265 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.15 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719152/	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	CHIR-265 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.26 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719152/	36 mg single, oral dose: 36 mg route of administration: Oral experiment type: SINGLE co-administered:	CHIR-265 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.54 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719152/	72 mg single, oral dose: 72 mg route of administration: Oral experiment type: SINGLE co-administered:	CHIR-265 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1.06 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719152/	144 mg single, oral dose: 144 mg route of administration: Oral experiment type: SINGLE co-administered:	CHIR-265 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.31 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719152/	288 mg single, oral dose: 288 mg route of administration: Oral experiment type: SINGLE co-administered:	CHIR-265 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.68 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719152/	403 mg single, oral dose: 403 mg route of administration: Oral experiment type: SINGLE co-administered:	CHIR-265 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.13 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719152/	10 mg 1 times / day steady-state, oral dose: 10 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	CHIR-265 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.12 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719152/	20 mg 1 times / day steady-state, oral dose: 20 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	CHIR-265 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.2 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719152/	36 mg 1 times / day steady-state, oral dose: 36 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	CHIR-265 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.42 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719152/	72 mg 1 times / day steady-state, oral dose: 72 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	CHIR-265 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.85 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719152/	144 mg 1 times / day steady-state, oral dose: 144 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	CHIR-265 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1.65 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719152/	288 mg 1 times / day steady-state, oral dose: 288 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	CHIR-265 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.65 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719152/	403 mg 1 times / day steady-state, oral dose: 403 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	CHIR-265 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.31 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719152/	288 mg 1 times / day multiple, oral dose: 288 mg route of administration: Oral experiment type: MULTIPLE co-administered:	RAF-265 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1.65 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719152/	48 mg 1 times / day steady-state, oral dose: 48 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	RAF-265 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
6.2 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719152/	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	CHIR-265 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
8.77 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719152/	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	CHIR-265 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
12.1 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719152/	36 mg single, oral dose: 36 mg route of administration: Oral experiment type: SINGLE co-administered:	CHIR-265 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
22.6 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719152/	72 mg single, oral dose: 72 mg route of administration: Oral experiment type: SINGLE co-administered:	CHIR-265 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
51.8 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719152/	144 mg single, oral dose: 144 mg route of administration: Oral experiment type: SINGLE co-administered:	CHIR-265 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
99.8 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719152/	288 mg single, oral dose: 288 mg route of administration: Oral experiment type: SINGLE co-administered:	CHIR-265 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
137 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719152/	403 mg single, oral dose: 403 mg route of administration: Oral experiment type: SINGLE co-administered:	CHIR-265 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.67 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719152/	10 mg 1 times / day steady-state, oral dose: 10 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	CHIR-265 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.3 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719152/	20 mg 1 times / day steady-state, oral dose: 20 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	CHIR-265 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4.15 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719152/	36 mg 1 times / day steady-state, oral dose: 36 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	CHIR-265 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
8.59 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719152/	72 mg 1 times / day steady-state, oral dose: 72 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	CHIR-265 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
16.1 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719152/	144 mg 1 times / day steady-state, oral dose: 144 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	CHIR-265 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
28.5 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719152/	288 mg 1 times / day steady-state, oral dose: 288 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	CHIR-265 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
46.8 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719152/	403 mg 1 times / day steady-state, oral dose: 403 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	CHIR-265 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
99.8 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719152/	288 mg 1 times / day multiple, oral dose: 288 mg route of administration: Oral experiment type: MULTIPLE co-administered:	RAF-265 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
28.5 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719152/	48 mg 1 times / day steady-state, oral dose: 48 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	RAF-265 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
287 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719152/	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	CHIR-265 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
209 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719152/	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	CHIR-265 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
127 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719152/	36 mg single, oral dose: 36 mg route of administration: Oral experiment type: SINGLE co-administered:	CHIR-265 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
174 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719152/	72 mg single, oral dose: 72 mg route of administration: Oral experiment type: SINGLE co-administered:	CHIR-265 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
182 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719152/	144 mg single, oral dose: 144 mg route of administration: Oral experiment type: SINGLE co-administered:	CHIR-265 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
183 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719152/	288 mg single, oral dose: 288 mg route of administration: Oral experiment type: SINGLE co-administered:	CHIR-265 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
294 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719152/	403 mg single, oral dose: 403 mg route of administration: Oral experiment type: SINGLE co-administered:	CHIR-265 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
183 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719152/	288 mg 1 times / day multiple, oral dose: 288 mg route of administration: Oral experiment type: MULTIPLE co-administered:	RAF-265 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
183 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28719152/	48 mg 1 times / day steady-state, oral dose: 48 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	RAF-265 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
1% EXPERIMENT https://pubs.acs.org/doi/full/10.1021/ml500526p	single, unknown		CHIR-265 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

PubMed

Title	Date	PubMed
Comprehensive analysis of kinase inhibitor selectivity.	2011-10-30	22037378
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.	2010-11-24	21095574
Dependence on phosphoinositide 3-kinase and RAS-RAF pathways drive the activity of RAF265, a novel RAF/VEGFR2 inhibitor, and RAD001 (Everolimus) in combination.	2010-02	20124452

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 `Mon Mar 31 18:26:35 GMT 2025` Edited by `admin` on `Mon Mar 31 18:26:35 GMT 2025`
Record UNII	8O434L3768
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

NVP-RAF265

Preferred Name

English

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

RAF265

Code

English

RAF 265 [WHO-DD]

Common Name

English

CHIR-265

Code

English

Code System Code Type Description

EPA CompTox

DTXSID601025871