RAF265(CHIR-265) Chemical Properties

Boiling point:

667.6±65.0 °C(Predicted)

Density 

1.50

storage temp. 

Store at -20°C

solubility 

≥25.9 mg/mL in DMSO; insoluble in H2O; ≥7.97 mg/mL in EtOH with ultrasonic

pka

9.07±0.27(Predicted)

form 

Solid

color 

White to khaki

Sensitive 

Light Sensitive

RAF265(CHIR-265) Usage And Synthesis

Description

RAF265, also known as (CHIR-265), is an arylaminobenzimidazole-based B-RAF, C-RAF, and VEGFR2 inhibitor developed by Chiron Corporation, later acquired by Novartis. 

Biological Activity

RAF265 is a novel, orally active, small molecule with potent inhibitory activity against B-Raf kinase and additional antiangiogenic activity through inhibition of vascular endothelial growth factor receptor type 2 (VEGFR-2) in non-clinical studies.

Uses

RAF265 (CHIR-265) is an oral, highly selective RAF and VEGFR kinase inhibitor with IC50 of of 5 to 10 μM.

Uses

RAF 265 is a multikinase inhibitor that has displayed BRAF inhibiting activity in clinical trials. It could be used in the treatment of a subpopulation of human melanoma tumors. Has cytotoxic effect of on MDA-MB-231 cells. RAF265 when used with BEZ-235 inhibited ERK, PI3K signaling that reduced growth, proliferation and development of drug resistance in human thyroid cancer cells.

Definition

ChEBI: 1-methyl-5-[[2-[5-(trifluoromethyl)-1H-imidazol-2-yl]-4-pyridinyl]oxy]-N-[4-(trifluoromethyl)phenyl]-2-benzimidazolamine is an aromatic ether.

Biological Activity

raf265, also known as chir-265, is a novel and orally available small molecule inhibitor of multiple intracellular kinases, including brafv600e, braf (wild-type), c-raf, vascular endothelial growth factor receptor 2 (vegfr2), platelet-derived growth factor receptor (pdgfr), colony-stimulating factor (csf) 1r, ret, c-kit, src and ste20, with half maximal inhibitory concentration ic50 ranging from less than 20 nmo/l to more than 100 nmol/l, in which it exhibits the highest potency for brafv600e and vegfr2 with half maximal effective concentration ec50 of 0.14 μm and 0.19 μm respectively. raf265 has been found to inhibit proliferation of melanoma and colorectal cancer cell lines with active braf mutations and time- and dose-dependently suppress tumor regression in brafv600e melanoma and colorectal cancer xenograft models.

target

B-Raf

References

[1]huang t1, karsy m, zhuge j, zhong m, liu d. b-raf and the inhibitors: from bench to bedside. j hematol oncol. 2013 apr 25;6:30. doi: 10.1186/1756-8722-6-30.
[2]garcia-gomez a1, ocio em, pandiella a, san miguel jf, garayoa m. raf265, a dual braf and vegfr2 inhibitor, prevents osteoclast formation and resorption. therapeutic implications. invest new drugs. 2013 feb;31(1):200-5. doi: 10.1007/s10637-012-9845-3. epub 2012 jul 7.
[3]su y1, vilgelm ae, kelley mc, hawkins oe, liu y, boyd kl, kantrow s, splittgerber rc, short sp, sobolik t, zaja-milatovic s, dahlman kb, amiri ki, jiang a, lu p, shyr y, stuart dd, levy s, sosman ja, richmond a. raf265 inhibits the growth of advanced human melanoma tumors. clin cancer res. 2012 apr 15;18(8):2184-98. doi: 10.1158/1078-0432.ccr-11-1122. epub 2012 feb 20.

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