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.
1 Customer Review
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.
Purity & Quality Control
Choose Selective MEK Inhibitors
|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. Phase 3.|
GDC-0973 shows strong cellular potency in a broad panel of tumor types, particularly in BRAF (with most of EC50 below 2 μM) or KRAS mutant cancer cell lines. In a panel of cancer cell lines, 80% of BRAF mutant lines (including V600E and non-V600E mutations) are sensitive to GDC-0973, 54% of lines carrying oncogenic mutations in KRAS or NRAS are sensitive, and 35% of the remaining lines are sensitive. GDC-0941 and GDC-0973 act cooperatively to inhibit the viability of all melanoma cell lines tested, 60% of which carry oncogenic mutations in BRAF. Combination of GDC-0941(0.2 μM) and GDC-0973 (10 μM) almost completely suppresses the vitality of 888MEL (BRAFV600E) mutant melanoma cell lines at 4 day. Treatment with GDC-0973 and GDC-0941 results in a combinatorial increase of cellular mediators of apoptosis, such as cleaved PARP and alternatively spliced isoforms of Bim. Transient treatment of 888MEL cells with either single agent GDC-0973 or GDC-0941 results in minimal to no apoptosis induction, whereas GDC-0973 plus GDC-0941 results in a 5-fold increase in apoptosis. 
|In vivo||GDC-0973 shows activity in a number of human tumor xenograft models, particularly in models mutant for BRAF. GDC-0973 (5 mg/kg) leads to strong TGI (106%) in the A375.X1 BRAFV600E mutant melanoma xenograft model, accompanied with ~65% p-ERK suppression at 2, 8, and 24 hours. The combination of GDC-0973 (3mg/kg) and GDC-0941 (100mg/kg) leads to a greater tumor response rate for the A375 (BRAFV600E) model, as GDC-0973 results in 70% (7/10) complete responses (CR), GDC-0941 shows lack of TGI, whereas the combination results in 100% (10/10) CRs. |
|In vitro||DMSO||100 mg/mL (188.21 mM)|
|Ethanol||47 mg/mL warmed (88.46 mM)|
|In vivo||Add solvents individually and in order:
5% DMSO+30% PEG 300+5% Tween 80+ddH2O
* 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.
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).
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).
Molecular Weight Calculator
Enter the chemical formula of a compound to calculate its molar mass and elemental composition:
Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2
Instructions to calculate molar mass (molecular weight) of a chemical compound:
To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.
Definitions of molecular mass, molecular weight, molar mass and molar weight:
Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
Clinical Trial Information
|NCT Number||Recruitment||Conditions||Sponsor/Collaborators||Start Date||Phases|
|NCT02908672||Recruiting||Melanoma||Hoffmann-La Roche||January 2017||Phase 3|
|NCT03005639||Recruiting||Stage IIIB-C Melanoma||Inova Health Care Services|Genentech, Inc.||December 2016||Phase 2|
|NCT02968303||Not yet recruiting||Melanoma, Malignant, of Soft Parts||Radboud University|The Netherlands Cancer Institute|Isala||December 2016||Phase 2|
|NCT02902029||Recruiting||Malignant Melanoma||University Hospital, Essen||November 2016||Phase 2|
|NCT02876224||Recruiting||Colorectal Cancer||Hoffmann-La Roche||September 2016||Phase 1|
|NCT02721459||Recruiting||Melanoma|Skin Cancer||H. Lee Moffitt Cancer Center and Research Institute|Exelixis|Genentech, Inc.||August 2016||Phase 1|
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.
Tel: +1-832-582-8158 Ext:3
If you have any other enquiries, please leave a message.