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.
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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.
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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.
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Frequently Asked Questions
How to reconstitute the inhibitor for in vivo studies?
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.