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Cobimetinib (GDC-0973)

Name: Cobimetinib (GDC-0973)
Brand: Selleck Chemicals
SKU: S8041
Rating: 5 (73 reviews)

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 73 publications

Purity & Quality Control

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MEK Signaling Pathway Map

Biological Activity

Description

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	NVn4cGpJWHKxbHnm[ZJifGmxbjDhd5NigQ>?		NIjqS2tCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFPPUG8zODViY3XscJMh\XiycnXzd4lv\yCELYLh[kBXPjByRTDteZRidnRuIFnDOVA:QCCwTR?=	NV\1bphwRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKzNVU{OzJpPkKyN\|E2OzN{PD;hQi=>
human COLO205 cells	MU\GeY5kfGmxbjDhd5NigQ>?		NFvpUlNKdmirYnn0bY9vKG:oIFKtdoFnKFZ4MEDFJI12fGGwdDDpckBpfW2jbjDDU2xQOjB3IHPlcIx{KGG\|c3Xzd4VlKGG\|IILl[JVkfGmxbjDv[kBGWktzL1XST\|IheGixc4Doc5J6dGG2aX;uMEBKSzVyPUGuPEBvVQ>?	MmDBQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ\|MUWzN\|IoRjJ{M{G1N\|MzRC:jPh?=
human MDA-MB-231T cells	Mn7rSpVv[3Srb36gZZN{[Xl?	MXGxJIg>	MlfOTY5pcWKrdHnvckBw\iCPRVutcYVlcWG2ZXSgSXJMKFR{MEKvXVIxPCCyaH;zdIhwenmuYYTpc44hcW5iaIXtZY4hVUSDLV3CMVI{OVRiY3XscJMh[W[2ZYKgNUBpeiCkeTDpcY12dm:kbH;0eIlv\+,:jDDJR\|UxRTBwMjDuUS=>	MWC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlyMES4Okc,OjR7MEC0PFY9N2F-

Click to View More Cell Line Experimental Data

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.

References

Solubility (25°C)

In vitro


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. Click to purchase: PEG300 Tween 80	5mg/mL

Chemical Information

Molecular Weight	531.31
Formula	C₂₁H₂₁F₃IN₃O₂
CAS No.	934660-93-2
Storage	3 years	-20°C	powder
Storage	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

Download Cobimetinib (GDC-0973) SDF

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.

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

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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