Name: Avutometinib (Ro 5126766)
Brand: Selleck Chemicals
SKU: S7170
Availability: InStock
Rating: 5 (21 reviews)

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Quality Control

Batch: Purity: 99.54%

99.54

Related Targets	ERK p38 MAPK K-Ras JNK MEK Ras S6 Kinase MAP4K TAK1 Mixed Lineage Kinase
Other Raf Products	LY3009120 GDC-0879 Exarafenib PLX-4720 AZ 628 SB590885 TAK-632 RAF265 (CHIR-265) GW5074 PLX7904

Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Concentration	Incubation Time	Activity Description	PMID
HCT116 cell	Function assay		96 h	Inhibition of human HCT116 cell growth after 96 hrs by counting kit-8 analysis, IC50=0.04 μM	24900832
human C32 cells	Growth inhibition assay			Growth inhibition of human C32 cells harboring R-Raf V600E mutant, IC50=0.047 μM	24900832
human PANC1 cells	Function assay	10 μM	1 h	Inhibition of MEK1 in human PANC1 cells assessed as reduction in pErk1/2 level at 10 uM after 1 hr by Western blotting analysis	25766633
human A549 cells	Function assay	10 μM	1 h	Inhibition of MEK1 in human A549 cells assessed as reduction in pErk1/2 level at 10 uM after 1 hr by Western blotting analysis	25766633
Click to View More Cell Line Experimental Data

Solubility

In vitro
Batch:

DMSO : 94 mg/mL (199.38 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5% DMSO 1 45% PEG 300 2 ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	1.000mg/ml (2.12mM)	Taking the 1 mL working solution as an example, add 50 μL of 20 mg/ml clarified DMSO stock solution to 450 μL PEG 300, mix evenly to clarify it; then continue to add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

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

Dosage: mg/kg

Average weight of animals: g

Dosing volume per animal: μL

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Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO

%

% Tween 80

% ddH₂O

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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.

Chemical Information, Storage & Stability

Molecular Weight	471.46	Formula	C₂₁H₁₈FN₅O₅S	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	946128-88-7	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	RO5126766,CH5126766,VS 6766, CKI-27, R-7304, RG-7304			Smiles	CC1=C(C(=O)OC2=C1C=CC(=C2)OC3=NC=CC=N3)CC4=C(C(=NC=C4)NS(=O)(=O)NC)F

Mechanism of Action

Targets/IC₅₀/Ki	BRAF V600E (cell-free assay) 8.2 nM BRAF (cell-free assay) 19 nM CRAF (cell-free assay) 56 nM MEK1 (cell-free assay) 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. 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.
Kinase Assay	MEK and RAF kinase enzyme assays
Kinase Assay	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). 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.
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. In the HCT116 (K-ras) and COLO205 (B-raf) mutant xenografts, CH5126766 (0.3 mg/kg) causes significant decreases in [18 F]FDG uptake. In the SK-MEL-2 xenograft model, RO5126766 also suppresses the tumor growth.
References	[1] https://pubmed.ncbi.nlm.nih.gov/23667175/ [2] https://pubmed.ncbi.nlm.nih.gov/24041012/ [3] https://pubmed.ncbi.nlm.nih.gov/25422890/

Applications

Methods	Biomarkers	Images	PMID
Western blot	p-MEKR / MEK / p-ERK / ERK / p27 / ppRB / pRB / Cyclin D1 / Cyclin E		25422890

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT06104488	Recruiting	Refractory Cancer\|CNS Tumors\|CNS Tumor Adult\|CNS Tumor Childhood\|MAP Kinase Family Gene Mutation\|NF1\|Plexiform Neurofibroma\|Low-grade Glioma\|Optic Pathway Gliomas\|Neuroblastoma\|Primary Brain Tumor\|Solid Tumor\|Solid Tumor Adult\|Solid Carcinoma\|Central Nervous System Tumor	Memorial Sloan Kettering Cancer Center	October 20 2023	Phase 1
NCT05375994	Recruiting	Non Small Cell Lung Cancer\|KRAS Activating Mutation\|Advanced Cancer\|Metastatic Cancer\|Malignant Neoplasm of Lung\|Malignant Neoplastic Disease	Verastem Inc.\|Mirati Therapeutics Inc.	August 1 2022	Phase 1\|Phase 2

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Avutometinib (Ro 5126766) RAF/MEK Inhibitor

Chemical Structure

Molecular Weight: 471.46