RO5126766 (CH5126766)

Catalog No.S7170 Synonyms: VS 6766, CKI-27, R-7304, RG-7304

For research use only.

RO5126766 (CH5126766, VS 6766, CKI-27, R-7304, RG-7304) is a dual RAF/MEK inhibitor with IC50 of 8.2 nM,19 nM, 56 nM, and 160 nM for BRAF V600E, BRAF, CRAF, and MEK1, respectively. Phase 1.

RO5126766 (CH5126766) Chemical Structure

CAS No. 946128-88-7

Selleck's RO5126766 (CH5126766) has been cited by 12 Publications

Purity & Quality Control

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Biological Activity

Description RO5126766 (CH5126766, VS 6766, CKI-27, R-7304, RG-7304) is a dual RAF/MEK inhibitor with IC50 of 8.2 nM,19 nM, 56 nM, and 160 nM for BRAF V600E, BRAF, CRAF, and MEK1, respectively. Phase 1.
Targets
BRAF V600E [1]
(cell-free assay)
BRAF [1]
(cell-free assay)
CRAF [1]
(cell-free assay)
MEK1 [1]
(cell-free assay)
8.2 nM 19 nM 56 nM 160 nM
In vitro

In HCT116 KRAS-mutant colorectal cancer cells, CH5126766 significantly reduces the levels of phospho-MEK and phospho-ERK. CH5126766 inhibits RAF kinase by binding to MEK1, and causes MEK to become a dominant negative inhibitor of RAF. [1] In Raf or RAS-mutant cell lines SK-MEL-28, SK-MEL-2, MIAPaCa-2, SW480, HCT116, and PC3 cells, CH5126766 inhibits cell growth with IC50 of 65, 28, 40, 46, and 277 nM, respectively. In two melanoma cell lines with the BRAF V600E or NRAS mutation, RO5126766 induces G1 cell cycle arrest accompanied by up-regulation of the CDK inhibitor p27 and down-regulation of cyclinD1. [3]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
HCT116 cell M3TwZmZ2dmO2aX;uJIF{e2G7 M4rXZVk3KGh? NVr4bHBVUW6qaXLpeIlwdiCxZjDoeY1idiCKQ2SxNVYh[2WubDDndo94fGhiYX\0[ZIhQTZiaILzJIJ6KGOxdX70bY5oKGurdD24JIFv[Wy7c3nzMEBKSzVyPUCuNFQh|ryP MlPyQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7MEC4N|IoRjJ2OUCwPFMzRC:jPh?=
human C32 cells M1zKZmdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 M2\q[mdzd3e2aDDpcohq[mm2aX;uJI9nKGi3bXHuJGM{OiClZXzsd{Bp[XKkb4LpcochWi2UYX[gWlYxOEVibYX0ZY51NCCLQ{WwQVAvODR5IN88US=> M4fwWlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUCwPFMzLz5{NEmwNFg{OjxxYU6=
human PANC1 cells M{[0NGZ2dmO2aX;uJIF{e2G7 MlWwNVAh|ryP NFT1SWIyKGh? MVrJcohq[mm2aX;uJI9nKE2HS{GgbY4hcHWvYX6gVGFPSzFiY3XscJMh[XO|ZYPz[YQh[XNicnXkeYN1cW:wIHnuJJBGemtzL{KgcIV3\WxiYYSgNVAhfU1iYX\0[ZIhOSCqcjDifUBY\XO2ZYLuJIJtd3S2aX7nJIFv[Wy7c3nz MlXWQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV5Nk[2N|MoRjJ3N{[2OlM{RC:jPh?=
human A549 cells NYLTdlBnTnWwY4Tpc44h[XO|YYm= M3jtbFExKM7:TR?= MWSxJIg> NXLsPYxQUW6qaXLpeIlwdiCxZjDNSWsyKGmwIHj1cYFvKEF3NEmgZ4VtdHNiYYPz[ZN{\WRiYYOgdoVlfWO2aX;uJIlvKHCHcnuxM|IhdGW4ZXygZZQhOTBidV2gZYZ1\XJiMTDodkBjgSCZZYP0[ZJvKGKub4T0bY5oKGGwYXz5d4l{ NVTK[oxoRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW3OlY3OzNpPkK1O|Y3PjN|PD;hQi=>
Assay
Methods Test Index PMID
Western blot p-MEKR / MEK / p-ERK / ERK / p27 / ppRB / pRB / Cyclin D1 / Cyclin E 25422890
In vivo In an HCT116 (G13D KRAS) mouse xenograft model, CH5126766 (25 mg/kg, p.o.) inhibits ERK signaling output more effectively than a standard MEK inhibitor that induces MEK phosphorylation and has potent antitumor activity. [1] In the HCT116 (K-ras) and COLO205 (B-raf) mutant xenografts, CH5126766 (0.3 mg/kg) causes significant decreases in [18 F]FDG uptake. [2] In the SK-MEL-2 xenograft model, RO5126766 also suppresses the tumor growth. [3]

Protocol (from reference)

Kinase Assay:[1]
  • MEK and RAF kinase enzyme assays:

    The inhibitory activities against CRAF, BRAF, or BRAF V600E enzymes are measured by quantification of phosphorylation of inactive K97R MEK1 [MEK1] by recombinant RAF proteins [BRAF: B-RAF wt, BRAF V600E: B-RAF V600E or CRAF: Raf-1] with Europium-anti-MEK1/2 (pSer218/222) antibody and SureLight allophycocyanine-anti-6his antibody by measuring time-resolved fluorescence (TRF). Alternatively, the inhibitory activities against the RAF enzymes are measured by quantification of phosphorylation of a fluorescein-labeled peptide corresponding to human MEK1 212-224 and human MEK2 217-229 (5-Fl-SGQLIDSMANSFV-NH2, MEKtide) by using the IMAP fluorescence polarization (FP) Screening Express Kit. Inhibition of MEK1 is evaluated by a coupled assay with active MEK1 (MEK1 S218E/S222E) and unactive dephosphorylated ERK2 (MAP kinase 2/Erk 2). The phosphorylation of a fluorescent-labeled peptide substrate (FAM-Erktide, IPTTPITTTYFFFK-5FAM-COOH) by ERK2 is quantified by using the IMAP FP Screening Express Kit.

Cell Research:[3]
  • Cell lines: SK-MEL-28, SK-MEL-2, MIAPaCa-2, SW480, A549, HCT15, HCT116, and PC3 cells
  • Concentrations: ~10 μM
  • Incubation Time: 72 h
  • Method: The number of viable cells is determined using the Cell Counting Kit-8 assay according to the manufacturer's instructions. After the incubation of cells for 72 h with the indicated concentrations of various agents, kit reagent WST-8 is added to the medium and incubated for a further 4 h. The absorbance of samples (450 nm) is determined using a scanning multiwell spectrophotometer that serves as an ELISA reader. Cell numbers and viability are also measured using the ViaCount Assay according to the manufacturer's instructions.
Animal Research:[1]
  • Animal Models: Female BALB-nu/nu mice bearing HCT116, Calu-6 or COLO205 tumors
  • Dosages: ~25 mg/kg
  • Administration: p.o.

Solubility (25°C)

In vitro

DMSO 94 mg/mL
(199.38 mM)
Water Insoluble
Ethanol Insoluble

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
5% DMSO+45% PEG 300+ddH2O
For best results, use promptly after mixing.

20mg/mL

Chemical Information

Molecular Weight 471.46
Formula

C21H18FN5O5S

CAS No. 946128-88-7
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CC1=C(C(=O)OC2=C1C=CC(=C2)OC3=NC=CC=N3)CC4=C(C(=NC=C4)NS(=O)(=O)NC)F

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

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%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT03875820 Recruiting Drug: RO5126766|Drug: VS-6063 NSCLC|Solid Tumor|Low Grade Serous Ovarian Cancer|Colorectal Cancer Institute of Cancer Research United Kingdom|Verastem Inc.|Chugai Pharmaceutical December 12 2017 Phase 1
NCT02407509 Recruiting Drug: RO5126766|Drug: Everolimus Solid Tumours|Multiple Myeloma Royal Marsden NHS Foundation Trust|Institute of Cancer Research United Kingdom|Chugai Pharmaceutical June 17 2013 Phase 1

(data from https://clinicaltrials.gov, updated on 2022-01-17)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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