Cobimetinib (GDC-0973, RG7420)

Catalog No.S8041 Synonyms: XL518

Molecular Weight(MW): 531.31

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. Phase 3.

3 Customer Reviews

Three types of selective inhibitors of MAPK signaling produce expected differential kinase inhibition and activation responses in HCT116 colorectal cancer cells. HCT116 cells were treated with 250 nM of GDC-0973, GDC-0623, SCH772984 or DMSO for 1, 4, or 24 h. In the washout samples, cells were drug treated for 24 h, then changed into fresh media and harvested after 0.5 or 2 h. Lysates were used for Western blots of total and phosphorylated MEK, ERK, and RSK; blotting for COX IV was used as the loading control.

Mol Cell Proteomics, 2017, 16(2):265-277. Cobimetinib (GDC-0973, RG7420) purchased from Selleck.

Western blots showing protein changes of p21, p53, cyclin D1, and cyclin E in HCT116 cells after treatment with 1 μM cobimetinib over different timespans.

Cell Physiol Biochem, 2018, 47(2):680-693. Cobimetinib (GDC-0973, RG7420) purchased from Selleck.
Human-washed platelet aggregation was performed by optical aggregometry following stimulation with U46619 (0.25μM) in the presence or absence of LPS from E. coli O111:B4 (1μg/mL) after 3 min of incubation with Cobimetinib (100μM) before activation with U46619 (0.25μM) (B).

PLoS One, 2017, 12(11):e0186981. Cobimetinib (GDC-0973, RG7420) purchased from Selleck.

Purity & Quality Control

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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	Incubation Time	Activity Description	PMID
human MDA-MB-231T cells	MmPISpVv[3Srb36gZZN{[Xl?	MlTENUBp	MkHxTY5pcWKrdHnvckBw\iCPRVutcYVlcWG2ZXSgSXJMKFR{MEKvXVIxPCCyaH;zdIhwenmuYYTpc44hcW5iaIXtZY4hVUSDLV3CMVI{OVRiY3XscJMh[W[2ZYKgNUBpeiCkeTDpcY12dm:kbH;0eIlv\+,:jDDJR\|UxRTBwMjDuUS=>	NEjLXo8zPDlyMES4Oi=>
human COLO205 cells	NWTDeGlqTnWwY4Tpc44h[XO\|YYm=		NGKxXHhKdmirYnn0bY9vKG:oIFKtdoFnKFZ4MEDFJI12fGGwdDDpckBpfW2jbjDDU2xQOjB3IHPlcIx{KGG\|c3Xzd4VlKGG\|IILl[JVkfGmxbjDv[kBGWktzL1XST\|IheGixc4Doc5J6dGG2aX;uMEBKSzVyPUGuPEBvVQ>?	NICzNHQzOjNzNUOzNi=>
human COLO205 cells	MojsVJJwdGmoZYLheIlwdiCjc4PhfS=>		NH\TUINCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFPPUG8zODViY3XscJMh\XiycnXzd4lv\yCELYLh[kBXPjByRTDteZRidnRuIFnDOVA:QCCwTR?=	M2HFclIzOzF3M{Oy

... Click to View More Cell Line Experimental Data

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

Animal Research: ^[1]	+ Expand 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 Formulation: -- Dosages: 10 mg/kg Administration: p.o. (Only for Reference)

References

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 Download Cobimetinib (GDC-0973, RG7420) SDF

Molecular Weight	531.31
Formula	C₂₁H₂₁F₃IN₃O₂
CAS No.	934660-93-2
Storage	3 years -20°C powder
Storage	2 years -80°C in solvent
Synonyms	XL518

Bio Calculators

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration _(start) x Volume _(start) = Concentration _(final) x Volume _(final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).

The Serial Dilution Calculator Equation

Serial Dilutions
Concertration (start):
Dilution-folds:

Computed Result

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

Molecular Weight Calculator

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Molarity Calculator

Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2018-11-16)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT03732703	Not yet recruiting	Relapsed Refractory Multiple Myeloma	Multiple Myeloma Research Foundation\|AbbVie\|Celgene Corporation\|Eli Lilly and Company\|Genentech Inc.\|Janssen LP\|Takeda\|Multiple Myeloma Research Consortium	December 10 2018	Phase 1\|Phase 2
NCT03695380	Not yet recruiting	OVARIAN CANCER	Hoffmann-La Roche	December 31 2018	Phase 1
NCT03625141	Not yet recruiting	Metastatic Melanoma	Hoffmann-La Roche	September 10 2018	Phase 2
NCT03498521	Recruiting	Cancer of Unknown Primary Site	Hoffmann-La Roche\|Foundation Medicine Inc.	July 10 2018	Phase 2
NCT03600701	Recruiting	Recurrent Non-Small Cell Lung Carcinoma\|Refractory Lung Non-Small Cell Carcinoma\|Stage IV Non-Small Cell Lung Cancer AJCC v7	National Cancer Institute (NCI)	July 20 2018	Phase 2
NCT03363867	Recruiting	Ovarian Cancer\|Fallopian Tube Cancer\|Primary Peritoneal Carcinoma	Peter MacCallum Cancer Centre Australia	July 10 2018	Phase 2

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

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 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.

MEK Signaling Pathway Map

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Cobimetinib (GDC-0973, RG7420)