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Cobimetinib (GDC-0973) MEK1 inhibitor

Name: Cobimetinib (GDC-0973)
Brand: Selleck Chemicals
SKU: S8041
Availability: InStock
Rating: 5 (111 reviews)

Cat.No.S8041

Cobimetinib (GDC-0973, RG7420) is a potent and highly selective MEK1 inhibitor with IC50 of 4.2 nM, showing no significant inhibition when tested against a panel of more than 100 serine-threonine and tyrosine kinases. This compound induces apoptosis. Phase 3.

Chemical Structure

Molecular Weight: 531.31

Jump to Mechanism of Action Cell Culture & Working Concentration Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Batch: Purity: 99.86%

99.86

Related Targets	Ras ERK p38 MAPK Raf JNK S6 Kinase MAP4K TAK1 Mixed Lineage Kinase ASK MNK MAPKAPK2 KLF TOPK
Related Products	PD0325901 (Mirdametinib) U0126-EtOH PD98059 PD184352 (CI-1040) BIX 02189 Pimasertib (AS-703026) Refametinib (RDEA119) TAK-733 AZD8330 BIX 02188 GDC-0623 SL-327 Myricetin BI-847325 PD318088 APS-2-79 HCl MEK1 Antibody [F9N7] PD184161 Nedometinib MEK1 Antibody [G24C19] GW284543 (UNC10225170) RO4987655 Atebimetinib (IMM-1-104) MEK1/2 Antibody [J11P23] Zapnometinib (PD0184264) Tunlametinib Phospho-MEK1/2 (Ser217/221) Antibody [G6P21] Rap1B Antibody [H22K21] MEK2 Antibody [M18L8] Rap1A/Rap1B Antibody [E5J15]

Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Incubation Time	Activity Description	PMID
human COLO205 cells	Proliferation assay		Antiproliferative activity against human COLO205 cells expressing B-raf V600E mutant, IC50=8 nM	22315332
human COLO205 cells	Function assay		Inhibition of B-raf V600E mutant in human COLO205 cells assessed as reduction of ERK1/ERK2 phosphorylation, IC50=1.8 nM	22315332
human MDA-MB-231T cells	Function assay	1 h	Inhibition of MEK-mediated ERK T202/Y204 phosphorylation in human MDA-MB-231T cells after 1 hr by immunoblotting， IC50=0.2 nM	24900486
Click to View More Cell Line Experimental Data

Chemical Information, Storage & Stability

Molecular Weight	531.31	Formula	C₂₁H₂₁F₃IN₃O₂	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	934660-93-2	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	RG7420,XL518			Smiles	C1CCNC(C1)C2(CN(C2)C(=O)C3=C(C(=C(C=C3)F)F)NC4=C(C=C(C=C4)I)F)O

Solubility

In vitro
Batch:

DMSO : 100 mg/mL (188.21 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 47 mg/mL

Water : 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.
Clear solution	5%DMSO 1 30%PEG300 2 5%Tween80 3 60%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	5.000mg/ml (9.41mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 300 μL PEG300, mix evenly to clarify it; add 50 μL Tween80 to the above system, mix evenly to clarify it; then continue to add 600 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.
Clear solution	5%DMSO 1 Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	5.000mg/ml (9.41mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. 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.
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

Number of animals:

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

% 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.

Mechanism of Action

Targets/IC₅₀/Ki	MEK1 ^[1] (Cell-free assay) 4.2 nM
In vitro	Cobimetinib (GDC-0973) shows strong activity on cell growth inhibtion in a broad panel of tumor types, particularly in BRAF or KRAS mutant cancer cell lines. In combination with GDC-0941, it results in reduced viability, pathway inhibition, and increased apoptosis in 888MEL and A2058 cells. ^[1]
In vivo	In mice bearing BRAFV600E and KRAS mutant tumors, Cobimetinib (GDC-0973) (10 mg/kg, p.o.) produces antitumor efficacy, and the combination of this compound and GDC-0941 show improved efficacy. ^[1] In mice bearing drug-resistant A375 xenografts, the combination of it and GDC-0941 induces decreased levels of hexokinase II, c-RAF, Ksr and p-MEK protein. ^[2]
References	[1] https://pubmed.ncbi.nlm.nih.gov/22084396/ [2] https://pubmed.ncbi.nlm.nih.gov/22651703/

Applications

Methods	Biomarkers	Images	PMID
Western blot	pERK / ERK / MCL-1 / p-MCL1 / BIM / cleaved PARP p-c-RAF / c-RAF / p-MEK / MEK		27765849
Growth inhibition assay	Cell viability		28098866

Clinical Trial Information

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

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT05756556	Suspended	Melanoma\|Malignant Melanoma	ImmVira Pharma Co. Ltd	June 30 2024	Phase 2
NCT05768178	Recruiting	Solid Tumor\|Haematological Malignancy\|Melanoma\|Thyroid Cancer Papillary\|Ovarian Neoplasms\|Colorectal Neoplasms\|Laryngeal Neoplasms\|Carcinoma Non-Small-Cell Lung\|Glioma\|Multiple Myeloma\|Erdheim-Chester Disease\|Thyroid Carcinoma Anaplastic	Cancer Research UK\|University of Manchester\|University of Birmingham\|Royal Marsden NHS Foundation Trust\|Hoffmann-La Roche	March 1 2023	Phase 2\|Phase 3
NCT04835805	Active not recruiting	Melanoma	Genentech Inc.	May 13 2021	Phase 1
NCT04109456	Recruiting	Metastatic Melanoma	InxMed (Shanghai) Co. Ltd.	March 16 2020	Phase 1
NCT04007848	Completed	Disease or R Group Histiocytoses	Assistance Publique - Hôpitaux de Paris	July 25 2019	Phase 3
NCT03695380	Completed	OVARIAN CANCER	Hoffmann-La Roche	January 9 2019	Phase 1

Tech Support

Handling Instructions

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

Frequently Asked Questions

Question 1:
How to reconstitute it for in vivo studies?

Answer:
It can be dissolved in 5% DMSO/30% PEG 300/5% Tween 80/ddH2O at 5 mg/ml clearly and is suitable for both oral gavage and injection.

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