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RAF265

Cat. No. M1863
RAF265 Structure
Synonym:

CHIR-265

Size Price Availability Quantity
5mg USD 145 In stock
10mg USD 250 In stock
25mg USD 400 In stock
50mg USD 750 In stock
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Quality Control
Biological Activity

RAF265 (CHIR-265) is a novel, orally bioavailable dual inhibitor of RAF kinase and VEGFR2. RAF265 significantly enhanced TRAIL sensitivity in NCI-H727 and CM insulinoma cells by blocking Raf-MEK-Erk signalling. RAF265 strongly decreased Bcl-2 levels in those cell lines susceptible to its TRAIL-sensitizing action. RAF265 impaired in vitro differentiation of PBMCs to OCs induced by receptor activator of NF-kB ligand (RANKL) and M-CSF (IC(50) ≈ 160 nM). In parallel, RAF265 exerted a potent inhibition of OC resorptive capacity (IC(50) ≈ 20 nM). Moreover, RAF265 exhibits reduced pMEK1, reduced proliferation based upon reduced Ki-67, cyclin D1 and polo-like kinase1 levels, and induction of the apoptosis mediator BCL2-like 11. Using Raf-MEK-Erk pathway inhibitors and TRAIL together might offer a novel therapeutic strategy in NET disease.

Customer Product Validations & Biological Datas
Source Mol Cancer (2015). Figure 1.RAF265
Method MTT assay
Cell Lines HT29 and HCT116 cells
Concentrations 0–50 μM
Incubation Time 48 h
Results When treated with 1 μM Raf265 for 3 weeks, the number of colony formed reduced from 38.6 ± 6.5 and 28.3 ± 3.5 to 1.67 ± 1.15 and 0.67 ± 0.58 colonies for HT29 and HCT116 cells, respectively.
Protocol
Cell Experiment
Cell lines HCT116, HT29, and MDAMB231 cell lines
Preparation method Cell Viability Assay
The MTT assay and Bliss additivism model were used to assess the effect of the combination on cell viability. In each well of a 96-well plate, 1 × 104 cells were grown in 200 μL of medium. After 24 h, RAD001, RAF265, or the combination was added to achieve a final concentration of 0.1 to 10 nmol/L and 0.1 to 10 μmol/L, respectively. After 48 h of treatment, 20 μL of 5 mg mL−1 MTT (Organics Research, Inc.) solution in PBS was added to each well. After 4 h, supernatant was removed and formazan crystals were discarded in 200 μL of DMSO. Absorbance was then measured at 595 nm using an absorbance plate reader (Bio-Rad Microplate Reader). Data are expressed as the percentage of viable cells in treated relative to nontreated conditions.
Concentrations 0.1 to 10 μM
Incubation time 48 h
Animal Experiment
Animal models mice bearing HCT116, A549 or MDAMB231 xenografts
Formulation DMSO/PBS
Dosages 12 mg/kg daily over 14 d (6 d on, 2 d off, 6 d on)
Administration orally
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 518.41
Formula C24H16F6N6O
CAS Number 927880-90-8
Purity 99.29%
Solubility DMSO ≥100 mg/mL
Storage at -20°C
References

RAF265, a dual BRAF and VEGFR2 inhibitor, prevents osteoclast formation and resorption. Therapeutic implications.
Garcia-Gomez et al. Invest New Drugs. 2012 Jul 7. PMID: 22773056.

RAF265 inhibits the growth of advanced human melanoma tumors.
Su et al. Clin Cancer Res. 2012 Apr 15;18(8):2184-98. PMID: 22351689.

The novel Raf inhibitor Raf265 decreases Bcl-2 levels and confers TRAIL-sensitivity to neuroendocrine tumour cells.
Zitzmann et al. Endocr Relat Cancer. 2011 Mar 21;18(2):277-85. PMID: 21317202.

Dependence on phosphoinositide 3-kinase and RAS-RAF pathways drive the activity of RAF265, a novel RAF/VEGFR2 inhibitor, and RAD001 (Everolimus) in combination.
Mordant P, et al. Mol Cancer Ther. 2010 Feb;9(2):358-68. PMID: 20124452.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: RAF265, CHIR-265 supplier, Raf, inhibitors

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