927880-90-8

Basic information

• Product Name: RAF265(CHIR-265)
• Synonyms: RAF265(CHIR-265);RAF265;CHIR-265 or RAF265;1-Methyl-5-[[2-[5-(trifluoromethyl)-1H-imidazol-2-yl]-4-pyridinyl]oxy]-N-[4-(trifluoromethyl)phenyl]-1H-benzimidazol-2-amine;1-methyl-5-(2-(5-(trifluoromethyl)-1H-imidazol-2-yl)pyridin-4-yloxy)-N-(4-(trifluoromethyl)phenyl)-1H-benzo[d]imidazol-2-amine;1-Methyl-5-[[2-[5-(trifluoromethyl)-1H-imidazol-2-yl]-4-pyridinyl]oxy]-N-[4-(trifluoromethyl)phenyl]-1H-benzimidazol-2-amine RAF265 (CHIR-265);RAF 265 1-Methyl-5-[[2-[5-(trifluoromethyl)-1H-imidazol-2-yl]-4-pyridinyl]oxy]-N-[4-(trifluoromethyl)phenyl]-1H-benzimidazol-2-amine;1H-Benzimidazol-2-amine, 1-methyl-5-[[2-[5-(trifluoromethyl)-1H-imidazol-2-yl]-4-pyridinyl]oxy]-N-[4-(trifluoromethyl)phenyl]-
• CAS NO: 927880-90-8
• Molecular Formula: C₂₄H₁₆F₆N₆O
• Molecular Weight: 517.4059192
• EINECS: -0
• Product Categories: Inhibitors;MAPK
• Mol File: 927880-90-8.mol
• Article Data: 5

Chemical Properties

• Boiling Point: 667.6±65.0 °C(Predicted)
• Appearance: /
• Density: 1.50
• Solubility: ≥25.9 mg/mL in DMSO; insoluble in H2O; ≥7.97 mg/mL in EtOH with ultrasonic
• PKA: 9.07±0.27(Predicted)
• Sensitive: Light Sensitive
• CAS DataBase Reference: RAF265(CHIR-265)(CAS DataBase Reference)
• NIST Chemistry Reference: RAF265(CHIR-265)(927880-90-8)
• EPA Substance Registry System: RAF265(CHIR-265)(927880-90-8)

Safety Data

• Hazardous Substances Data: 927880-90-8(Hazardous Substances Data)

Usage

Description

RAF265 (CHIR-265) is an arylaminobenzimidazole-based B-RAF, C-RAF, and VEGFR2 inhibitor developed by Chiron Corporation, later acquired by Novartis. It is an oral, highly selective RAF and VEGFR kinase inhibitor with an IC50 of 5 to 10 μM.

Uses

Used in Oncology:
RAF265 (CHIR-265) is used as a multikinase inhibitor for the treatment of a subpopulation of human melanoma tumors. It has displayed BRAF inhibiting activity in clinical trials and has a cytotoxic effect on MDA-MB-231 cells.
Used in Combination Therapy for Thyroid Cancer:
RAF265 (CHIR-265) is used in combination with BEZ-235 to inhibit ERK and PI3K signaling, which reduces growth, proliferation, and development of drug resistance in human thyroid cancer cells.
Used in Drug Development:
RAF265 (CHIR-265) serves as a valuable compound in the development of targeted therapies for various cancer types, given its ability to inhibit multiple kinases involved in cancer cell growth and survival.

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.

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.

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.

Upstream product

• 927880-89-5 N₁-methyl-4-((2-(5-(trifluoromethyl)-1H-imidazol-2-yl)pyridin-4-yl)oxy)benzene-1,2-diamine 
• 1645-65-4 4-(trifluoromethyl)phenyl isothiocyanate 
• 431-35-6 3-bromo-1,1,1-trifluoroacetone 
• 611225-63-9 tert-butyl 4-(4-(methylamino)-3-nitrophenoxy)picolinate 
• 611226-24-5 (4-(4-(methylamino)-3-nitrophenoxy)pyridin-2-yl)methanol 
• 611226-25-6 4-(4-Methylamino-3-nitro-phenoxy)-pyridine-2-carbaldehyde 
• 610-81-1 4-hydroxy-2-nitroaniline 
• 611225-60-6 tert-butyl 4-(4-amino-3-nitrophenoxy)picolinate 
• 927880-88-4 N-methyl-2-nitro-4-((2-(5-(trifluoromethyl)-1H-imidazol-2-yl)pyridin-4-yl)oxy)aniline 

Downstream Products

• 927881-06-9 2-{4-[1-methyl-2-(4-trifluoromethyl-phenylamino)-1H-benzoimidazol-5-yloxy]-pyridin-2-yl}-3H-imidazole-4-carbonitrile 

Relevant articles and documents

Discovery of RAF265: A Potent mut-B-RAF inhibitor for the treatment of metastatic melanoma

Abrogation of errant signaling along the MAPK pathway through the inhibition of B-RAF kinase is a validated approach for the treatment of pathway-dependent cancers. We report the development of imidazo-benzimidazoles as potent B-RAF inhibitors. Robust in

SALTS OF BENZIMIDAZOLYL PYRIDYL ETHERS AND FORMULATIONS THEREOF

Salts of benzimidazolyl pyridyl ethers are provided, particularly salts of { 1 -methyl-5- [2-(5-trifluoromethyl- 1 H-imidazol-2-yl)-pyridin-4-yloxy] - 1 H-benzoimidazol-2-yl } -(4- trifluoromethyl-phenyl)amine. Compositions and formulations including such

Substituted benzimidazoles and methods of preparation

Methods for preparing new substituted benzimidazole compounds having formula (I) useful for treating kinase mediated disorders are provided wherein R1, R2, R3, R4, a, b, and c are defined herein