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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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Purity: ≥98%
Cobimetinib racemate is the racemic mixture of Cobimetinib (GDC-0973, RG7420; XL-518; Cotellic), which is a novel, orally bioavailable, highly potent and selective small-molecule MEK1 inhibitor with antitumor activity. With an IC50 of 4.2 nM, it inhibits MEK1. In order to treat melanoma, cobimetinib was approved in 2015 as an anti-cancer drug to be used alone, in combination with vemurafenib, or in combination with both vemurafenib and atezolizumab. Extracellular signal-related kinase 2 (ERK2) phosphorylation and activation are inhibited, and tumor cell proliferation is decreased as a result of GDC-0973's specific binding to and inhibition of the catalytic activity of MEK1.
| ln 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. GDC-0973 causes 888MEL and A2058 cells to undergo more apoptosis, pathway inhibition, and reduced viability when combined with GDC-0941. All BRAFV600E lines have increased levels of GLUT-1 on the cellular membrane following coadministration of GDC-0973 and vemurafenib.
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| ln Vivo |
Cobimetinib (10 mg/kg, p.o.) and GDC-0973 and GDC-0941 together exhibit improved antitumor efficacy in mice with BRAFV600E and KRAS mutant tumors. Combining GDC-0973 and GDC-0941 results in lower levels of hexokinase II, c-RAF, Ksr, and p-MEK protein in mice with drug-resistant A375 xenografts.
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| Enzyme Assay |
Cobimetinib (GDC-0973, RG7420) is a potent, selective and oral MEK1 inhibitor with an IC50 of 4.2 nM for MEK1.
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| Cell Assay |
For 888MEL and A2058 cells, cobimetinib (GDC-0973) has EC50 values of 0.2 M and 10 M, respectively. Treatment of melanoma cells with EC50 concentrations of MEK and PI3K inhibitors (888MEL: 0.05 μM GDC-0973, 2.5 μM GDC-0941; A2058: 2.5 μM GDC-0973, 2.5 μM GDC-0941) lasts for 24 hours. In melanoma with constitutive MAPK activation in A375 cells, mitochondrial OXPHOS regulates the amount of cell death brought on by cobimetinib (100 nM).
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| Animal Protocol |
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| References | |||
| Additional Infomation |
See also: Cobimetinib (annotation moved to).
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| Molecular Formula |
C21H21F3IN3O2
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| Molecular Weight |
531.31
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| Exact Mass |
531.063
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| CAS # |
934662-91-6
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| Related CAS # |
Cobimetinib;934660-93-2;Cobimetinib hemifumarate;1369665-02-0;Cobimetinib (R-enantiomer);934660-94-3;Cobimetinib-13C6 racemate
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| PubChem CID |
51038893
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| Appearance |
White to off-white solid
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| LogP |
4.12
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
30
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| Complexity |
624
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(N1CC(C2CCCCN2)(O)C1)C1C(NC2C(F)=CC(I)=CC=2)=C(F)C(F)=CC=1
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| InChi Key |
BSMCAPRUBJMWDF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H21F3IN3O2/c22-14-6-5-13(19(18(14)24)27-16-7-4-12(25)9-15(16)23)20(29)28-10-21(30,11-28)17-3-1-2-8-26-17/h4-7,9,17,26-27,30H,1-3,8,10-11H2
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| Chemical Name |
[3,4-difluoro-2-(2-fluoro-4-iodoanilino)phenyl]-(3-hydroxy-3-piperidin-2-ylazetidin-1-yl)methanone
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.71 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.71 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.71 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 5% DMSO+30% PEG 300+5% Tween 80+ddH2O: 5mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8821 mL | 9.4107 mL | 18.8214 mL | |
| 5 mM | 0.3764 mL | 1.8821 mL | 3.7643 mL | |
| 10 mM | 0.1882 mL | 0.9411 mL | 1.8821 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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 GDC-0973 is a selective, potent MEK inhibitor with efficacy in BRAF and RAS mutant cell lines. A, chemical structure of GDC-0973. B, GDC-0973 was tested in a panel of cell lines in 96-hour viability assays.Cancer Res.2012 Jan 1;72(1):210-9. |
 GDC-0973 single-agent efficacy and pharmacodynamic (PD) studies in BRAFV600Eand KRAS mutant tumor models. Dose-ranging efficacy studies were carried out in the (A) A375.X1 and (B) NCI-H2122 tumor xenograft models.Cancer Res.2012 Jan 1;72(1):210-9. |
 Combination of GDC-0973 + GDC-0941 results in reduced viability, pathway inhibition, and increased apoptosis. A, the 888MEL and A2058 BRAF mutant melanoma cell lines were treated with increasing concentrations of GDC-0973 and GDC-0941 as single agents and in combination and assayed in a 96-hour viability assay.Cancer Res.2012 Jan 1;72(1):210-9. |
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 GDC-0973 and GDC-0941 combination results in TGI when dosed daily.Cancer Res.2012 Jan 1;72(1):210-9. |
 GDC-0973 and GDC-0941 combination results in TGI when dosed intermittently.
Transient treatment of GDC-0973 + GDC-0941 results in apoptosis and prolonged accumulation of Bim. |
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