Cobimetinib (GDC-0973)

Catalog No.S8041 Synonyms: RG7420

For research use only.

Cobimetinib (GDC-0973, RG7420) is a potent and highly selective MEK1 inhibitor with IC50 of 4.2 nM, showing more than 100-fold selectively for MEK1 over MEK2 and showed no significant inhibition when tested against a panel of more than 100 of serine-threonine and tyrosine kinases. Cobimetinib induces apoptosis. Phase 3.

Cobimetinib (GDC-0973) Chemical Structure

CAS No. 934660-93-2

Selleck's Cobimetinib (GDC-0973) has been cited by 61 publications

Purity & Quality Control

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Biological Activity

Description Cobimetinib (GDC-0973, RG7420) is a potent and highly selective MEK1 inhibitor with IC50 of 4.2 nM, showing more than 100-fold selectively for MEK1 over MEK2 and showed no significant inhibition when tested against a panel of more than 100 of serine-threonine and tyrosine kinases. Cobimetinib induces apoptosis. Phase 3.
Targets
MEK1 [1]
(Cell-free assay)
4.2 nM
In vitro

Cobimetinib 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, GDC-0973 results in reduced viability, pathway inhibition, and increased apoptosis in 888MEL and A2058 cells. [1] Coadministration of GDC-0973 and vemurafenib significantly increases decreased levels of GLUT-1 on the cellular membrane across all BRAFV600E lines. [2]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human COLO205 cells NFe0NppRem:uaX\ldoF1cW:wIHHzd4F6 M3XtZmFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iQ1;MU|IxPSClZXzsd{BmgHC{ZYPzbY5oKEJvcnHmJHY3ODCHIH31eIFvfCxiSVO1NF05KG6P MkPYQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ|MUWzN|IoRjJ{M{G1N|MzRC:jPh?=
human COLO205 cells NVHUXYZzTnWwY4Tpc44h[XO|YYm= MXnJcohq[mm2aX;uJI9nKEJvcnHmJHY3ODCHIH31eIFvfCCrbjDoeY1idiCFT1zPNlA2KGOnbHzzJIF{e2W|c3XkJIF{KHKnZIXjeIlwdiCxZjDFVmsyN0WUS{KgdIhwe3Cqb4L5cIF1cW:wLDDJR|UxRTFwODDuUS=> NUfsOZR7RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKzNVU{OzJpPkKyN|E2OzN{PD;hQi=>
human MDA-MB-231T cells NYTMU25sTnWwY4Tpc44h[XO|YYm= MmXJNUBp MkjLTY5pcWKrdHnvckBw\iCPRVutcYVlcWG2ZXSgSXJMKFR{MEKvXVIxPCCyaH;zdIhwenmuYYTpc44hcW5iaIXtZY4hVUSDLV3CMVI{OVRiY3XscJMh[W[2ZYKgNUBpeiCkeTDpcY12dm:kbH;0eIlv\+,:jDDJR|UxRTBwMjDuUS=> NULMRXlGRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5NFA1QDZpPkK0PVAxPDh4PD;hQi=>
Assay
Methods Test Index PMID
Western blot pERK / ERK / MCL-1 / p-MCL1 / BIM / cleaved PARP ; p-c-RAF / c-RAF / p-MEK / MEK 27765849 26384788
Growth inhibition assay Cell viability 28098866
In vivo In mice bearing BRAFV600E and KRAS mutant tumors, Cobimetinib (10 mg/kg, p.o.) produces antitumor efficacy, and the combination of GDC-0973 and GDC-0941 show improved efficacy. [1] In mice bearing drug-resistant A375 xenografts, combination of GDC-0973 and GDC-0941 induces decreased levels of hexokinase II, c-RAF, Ksr and p-MEK protein. [2]

Protocol (from reference)

Animal Research:

[1]

  • Animal Models: Molm-13, Molm-16, MX-1, DLD-1, HCT-116, LoVo, FaDu, 537MEL, A2058, A2058-X1, A375, A375.X1, A427, A549, Calu-6, EBC-1, NCI-H441, NCI-H2122, NCI-H460, NCI-H520.X1, SKOV-3, KP4-X1.1, MiaPaCa-2, 22Rv1, DU-145.X1,S, NCI-H69 xenograft tumors in mice
  • Dosages: 10 mg/kg
  • Administration: p.o.
  • (Only for Reference)

Solubility (25°C)

In vitro

DMSO 100 mg/mL
(188.21 mM)
Ethanol 47 mg/mL warmed
(88.46 mM)
Water Insoluble

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
5% DMSO+30% PEG 300+5% Tween 80+ddH2O
For best results, use promptly after mixing.

5mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 531.31
Formula

C21H21F3IN3O2

CAS No. 934660-93-2
Storage 3 years -20°C powder
2 years -80°C in solvent
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

In vivo Formulation Calculator (Clear solution)

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

mg/kg g μL

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.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04835805 Recruiting Drug: Belvarafenib|Drug: Cobimetinib|Drug: Atezolizumab Melanoma Genentech Inc. May 13 2021 Phase 1
NCT04109456 Recruiting Drug: IN10018|Drug: Cobimetinib Metastatic Melanoma InxMed (Shanghai) Co. Ltd. March 16 2020 Phase 1
NCT04007848 Active not recruiting Drug: Cobimetinib|Drug: Placebo oral tablet Disease or R Group Histiocytoses Assistance Publique - Hôpitaux de Paris July 25 2019 Phase 3
NCT03695380 Active not recruiting Drug: Cobimetinib|Drug: Niraparib|Drug: Atezolizumab OVARIAN CANCER Hoffmann-La Roche January 9 2019 Phase 1
NCT03273153 Completed Drug: Cobimetinib|Drug: Atezolizumab|Drug: Pembrolizumab Advanced BRAFV600 Wild-type Melanoma Hoffmann-La Roche December 11 2017 Phase 3
NCT03312530 Completed Drug: Cobimetinib|Drug: Venetoclax|Drug: Atezolizumab Multiple Myeloma Hoffmann-La Roche November 13 2017 Phase 1|Phase 2

(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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Frequently Asked Questions

Question 1:
How to reconstitute the inhibitor for in vivo studies?

Answer:
S8041 can be dissolved in 5% DMSO/30% PEG 300/5% Tween 80/ddH2O at 5 mg/ml clearly and it is ok for both oral gavage and injection.

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