RAF265

Multiple intracellular kinases inhibitor CAS# 927880-90-8

RAF265

Catalog No. BCC3677----Order now to get a substantial discount!

Product Name & Size Price Stock
RAF265: 5mg $138 In Stock
RAF265: 10mg Please Inquire In Stock
RAF265: 20mg Please Inquire Please Inquire
RAF265: 50mg Please Inquire Please Inquire
RAF265: 100mg Please Inquire Please Inquire
RAF265: 200mg Please Inquire Please Inquire
RAF265: 500mg Please Inquire Please Inquire
RAF265: 1000mg Please Inquire Please Inquire
Related Products

Quality Control of RAF265

Number of papers citing our products

Chemical structure

RAF265

3D structure

Chemical Properties of RAF265

Cas No. 927880-90-8 SDF Download SDF
PubChem ID 11656518 Appearance Powder
Formula C24H16F6N6O M.Wt 518.43
Type of Compound N/A Storage Desiccate at -20°C
Synonyms CHIR-265
Solubility DMSO : ≥ 26 mg/mL (50.15 mM)
Ethanol : 10 mg/mL (19.29 mM; Need ultrasonic)
*"≥" means soluble, but saturation unknown.
Chemical Name 1-methyl-5-[2-[5-(trifluoromethyl)-1H-imidazol-2-yl]pyridin-4-yl]oxy-N-[4-(trifluoromethyl)phenyl]benzimidazol-2-amine
SMILES CN1C2=C(C=C(C=C2)OC3=CC(=NC=C3)C4=NC=C(N4)C(F)(F)F)N=C1NC5=CC=C(C=C5)C(F)(F)F
Standard InChIKey YABJJWZLRMPFSI-UHFFFAOYSA-N
Standard InChI 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)
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months.
Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it.
About Packaging 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial.
2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial.
3. Try to avoid loss or contamination during the experiment.
Shipping Condition Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request.

Biological Activity of RAF265

DescriptionRAF265 (CHIR-265) is a potent selective inhibitor of C-Raf/B-Raf/B-Raf V600E with IC50 of 3-60 nM.
TargetsB-RafVEGFR2    
IC503-60 nM30 nM (EC50)    

RAF265 Dilution Calculator

Concentration (start)
x
Volume (start)
=
Concentration (final)
x
Volume (final)
 
 
 
C1
V1
C2
V2

calculate

RAF265 Molarity Calculator

Mass
=
Concentration
x
Volume
x
MW*
 
 
 
g/mol

calculate

Preparing Stock Solutions of RAF265

1 mg 5 mg 10 mg 20 mg 25 mg
1 mM 1.9289 mL 9.6445 mL 19.289 mL 38.578 mL 48.2225 mL
5 mM 0.3858 mL 1.9289 mL 3.8578 mL 7.7156 mL 9.6445 mL
10 mM 0.1929 mL 0.9645 mL 1.9289 mL 3.8578 mL 4.8223 mL
50 mM 0.0386 mL 0.1929 mL 0.3858 mL 0.7716 mL 0.9645 mL
100 mM 0.0193 mL 0.0964 mL 0.1929 mL 0.3858 mL 0.4822 mL
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations.

Organizitions Citing Our Products recently

 
 
 

Calcutta University

University of Minnesota

University of Maryland School of Medicine

University of Illinois at Chicago

The Ohio State University

University of Zurich

Harvard University

Colorado State University

Auburn University

Yale University

Worcester Polytechnic Institute

Washington State University

Stanford University

University of Leipzig

Universidade da Beira Interior

The Institute of Cancer Research

Heidelberg University

University of Amsterdam

University of Auckland
TsingHua University
TsingHua University
The University of Michigan
The University of Michigan
Miami University
Miami University
DRURY University
DRURY University
Jilin University
Jilin University
Fudan University
Fudan University
Wuhan University
Wuhan University
Sun Yat-sen University
Sun Yat-sen University
Universite de Paris
Universite de Paris
Deemed University
Deemed University
Auckland University
Auckland University
The University of Tokyo
The University of Tokyo
Korea University
Korea University

Background on RAF265

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.

Featured Products
New Products
 

References on RAF265

Discovery of RAF265: A Potent mut-B-RAF Inhibitor for the Treatment of Metastatic Melanoma.[Pubmed:26396681]

ACS Med Chem Lett. 2015 Aug 3;6(9):961-5.

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 vivo efficacy coupled with correlating pharmacokinetic/pharmacodynamic (PKPD) and PD-efficacy relationships led to the identification of RAF265, 1, which has advanced into clinical trials.

Preclinical analysis of the anti-tumor and anti-metastatic effects of Raf265 on colon cancer cells and CD26(+) cancer stem cells in colorectal carcinoma.[Pubmed:25884645]

Mol Cancer. 2015 Apr 11;14:80.

BACKGROUND: In colorectal carcinoma (CRC), activation of the Raf/MEK/ERK signaling pathway is commonly observed. In addition, the commonly used 5FU-based chemotherapy in patients with metastatic CRC was found to enrich a subpopulation of CD26(+) cancer stem cells (CSCs). As activation of the Raf/MEK/ERK signaling pathway was also found in the CD26(+) CSCs and therefore, we hypothesized that an ATP-competitive pan-Raf inhibitor, RAF265, is effective in eliminating the cancer cells and the CD26(+) CSCs in CRC patients. METHODS: HT29 and HCT116 cells were treated with various concentrations of RAF265 to study the anti-proliferative and apoptotic effects of RAF265. Anti-tumor effect was also demonstrated using a xenograft model. Cells were also treated with RAF265 in combination with 5FU to demonstrate the anti-migratory and invasive effects by targeting on the CD26(+) CSCs and the anti-metastatic effect of the combined treatment was shown in an orthotopic CRC model. RESULTS: RAF265 was found to be highly effective in inhibiting cell proliferation and tumor growth through the inhibition of the RAF/MEK/ERK signaling pathway. In addition, anti-migratory and invasive effect was found with RAF265 treatment in combination with 5FU by targeting on the CD26(+) cells. Finally, the anti-tumor and anti-metastatic effect of RAF265 in combination with 5FU was also demonstrated. CONCLUSIONS: This preclinical study demonstrates the anti-tumor and anti-metastatic activity of RAF265 in CRC, providing the basis for exploiting its potential use and combination therapy with 5FU in the clinical treatment of CRC.

The combination of RAF265, SB590885, ZSTK474 on thyroid cancer cell lines deeply impact on proliferation and MAPK and PI3K/Akt signaling pathways.[Pubmed:24821574]

Invest New Drugs. 2014 Aug;32(4):626-35.

Papillary thyroid cancer (PTC) is the most frequent thyroid cancer entity, accounting for 88 % of cases. It may metastasize and loose iodine uptake capability, preventing any radioiodine or surgical treatment. The main gene altered in PTC is BRAF, which is found altered in over 50 % of cases. Moreover MAPK and PI3K/Akt pathways are greatly implicated in PTC development. Many target therapies for PTC are currently under investigation, unfortunately without the expected results. Aim of this study was to characterized the preclinical effectiveness of novel promising drugs, RAF265, SB590885 and ZSTK474 in 3 thyroid cancer cell lines (BCPAP, K1, 8505C). RAF265 and SB590885 target differentially BRAF, while ZSTK474 acts on PI3K. IC50 demonstrated high drug activities ranging from 0.1 to 6.2 muM, depending on drugs and cell type, while combination index revealed an interesting synergistic effect of combination regimen (RAF265 + ZSTK474 and SB590885 + ZSTK474) in almost all cell lines. Moreover this synergistic effect was particularly evident by Western blot, whereas dual MAPK and PI3K/Akt inhibition was detected. In addition, treating cells with SB590885 induced marked morphological changes, leading to massive vacuolization. This suggests an activation of apoptotic process, as underlined by Annexin V flow cytometry analysis. Also cell cycle was altered in treated cells, without evidence of a common pattern, but rather with a more specific effect relying on single drug or combination regimen used. Since beneficial effects of in vitro combination regimen (RAF265 + ZSTK474 and SB590885 + ZSTK474), it is recommended additional investigation. These data suggest the potential use of combination regimen in in vivo experiment or afterwards in human PTC.

Synergistic antitumour activity of RAF265 and ZSTK474 on human TT medullary thyroid cancer cells.[Pubmed:26081844]

J Cell Mol Med. 2015 Sep;19(9):2244-52.

Medullary thyroid cancer (MTC) is an aggressive malignancy responsible for up to 14% of all thyroid cancer-related deaths. It is characterized by point mutations in the rearranged during transfection (RET) proto-oncogene. The activated RET kinase is known to signal via extracellular signal regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K), leading to enhanced proliferation and resistance to apoptosis. In the present work, we have investigated the effect of two serine/threonine-protein kinase B-Raf (BRAF) inhibitors (RAF265 and SB590885), and a PI3K inhibitor (ZSTK474), on RET-mediated signalling and proliferation in a MTC cell line (TT cells) harbouring the RETC634W activating mutation. The effects of the inhibitors on VEGFR2, PI3K/Akt and mitogen-activated protein kinases signalling pathways, cell cycle, apoptosis and calcitonin production were also investigated. Only the RAF265+ ZSTK474 combination synergistically reduced the viability of treated cells. We observed a strong decrease in phosphorylated VEGFR2 for RAF265+ ZSTK474 and a signal reduction in activated Akt for ZSTK474. The activated ERK signal also decreased after RAF265 and RAF265+ ZSTK474 treatments. Alone and in combination with ZSTK474, RAF265 induced a sustained increase in necrosis. Only RAF265, alone and combined with ZSTK474, prompted a significant drop in calcitonin production. Combination therapy using RAF265 and ZSTK47 proved effective in MTC, demonstrating a cytotoxic effect. As the two inhibitors have been successfully tested individually in clinical trials on other human cancers, our preclinical data support the feasibility of their combined use in aggressive MTC.

Description

RAF265 is a potent RAF/VEGFR2 inhibitor.

Keywords:

RAF265,927880-90-8,CHIR-265,Natural Products,VEGFR, buy RAF265 , RAF265 supplier , purchase RAF265 , RAF265 cost , RAF265 manufacturer , order RAF265 , high purity RAF265

Online Inquiry for:

      Fill out the information below

      • Size:Qty: - +

      * Required Fields

                                      Result: