| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
MEK1 (IC50 = 4.2 nM)
Cobimetinib hemifumarate targets MEK1 (mitogen-activated protein kinase kinase 1), a key component of the RAS/RAF/MEK/ERK signaling pathway. MEK1 is a dual-specificity kinase that phosphorylates and activates ERK1/2, which regulate cell proliferation, survival, differentiation, and migration. The RAS/RAF/MEK/ERK pathway is frequently hyperactivated in cancer due to mutations in RAS or RAF, making MEK a key therapeutic target. Cobimetinib hemifumarate is a potent, selective MEK1 inhibitor with an IC50 of 4.2 nM. By blocking MEK1/2 activity, the compound inhibits tumor cell growth and proliferation. The hemifumarate salt form is used for pharmaceutical formulations. |
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| ln Vitro |
Cobimetinib (GDC-0973) has an EC50 of 0.2 μM and 10 μM for 888MEL and A2058 cells, respectively. (888MEL: 0.05 μM GDC-0973, 2.5 μM GDC-0941; A2058: 2.5 μM GDC-0973, 2.5 μM GDC-0941)[1] Melanoma cells are treated with EC50 concentrations of MEK and PI3K inhibitors for 24 hours. When cobimetinib (100 nM) is used to treat melanoma cells in A375 cells, mitochondrial OXPHOS limits the amount of cell death that is induced[4].
Cobimetinib hemifumarate demonstrates potent in vitro activity against MEK1 with an IC50 of 4.2 nM. The compound inhibits MEK1 and MEK2, key components of the MAPK/ERK signaling pathway. By blocking the activity of MEK1/2, Cobimetinib hemifumarate inhibits tumor cell growth and proliferation. The compound's potent MEK inhibition makes it a valuable tool for studying the role of the MAPK/ERK pathway in cancer and other diseases. The compound's activity has been characterized in various in vitro systems, confirming its mechanism of action as a MEK inhibitor. |
| ln Vivo |
Treatment with Cobimetinib (GDC-0973) up to 5 mg/kg causes moderate TGI in the NCI-H2122 KRASG12C mutant non-small cell lung carcinoma (NSCLC) xenograft model, and at 10 mg/kg approaches tumor stasis[1]. GDC-0973 and GDC-0941 are given to mice with the A2058 tumor daily (QD) or every third day (Q3D), either separately or together. For GDC-0973 and GDC-0941, the population rate constants linked to tumor growth inhibition are 0.00102 and 0000651 μM-1 h-1, respectively[2]. Based on tumor concentrations in xenografted mice, the estimated in vivo IC50 values of %pERK decrease are 0.78 (WM-266-4) and 0.52 μM (A375) after single doses of GDC-0973 (1, 3, or 10 mg/kg, p.o.)[3].
Cobimetinib hemifumarate has been evaluated in vivo for its antitumor activity. Cobimetinib (the active enantiomer) was approved by the FDA for the treatment of unresectable or metastatic melanoma with BRAF V600E or V600K mutations, used in combination with vemurafenib. In preclinical and clinical studies, Cobimetinib hemifumarate has demonstrated efficacy in suppressing tumor growth in BRAF-mutant melanoma. By blocking MEK1/2 activity, the compound inhibits tumor cell growth and proliferation. The compound's oral bioavailability supports its utility for in vivo studies. Detailed clinical efficacy data are available in the published literature. |
| Enzyme Assay |
Cobimetinib (GDC-0973, RG7420) is a potent, selective and oral MEK1 inhibitor with an IC50 of 4.2 nM for MEK1.
The in vitro enzyme inhibition assay for Cobimetinib hemifumarate measures the inhibition of MEK1 kinase activity. Recombinant human MEK1 enzyme is incubated with varying concentrations of Cobimetinib hemifumarate (typically ranging from nanomolar to micromolar) in the presence of ATP and ERK2 as a substrate. The kinase reaction is allowed to proceed for a fixed period, and the extent of ERK2 phosphorylation is quantified using techniques such as fluorescence polarization, luminescence-based kinase assays, or Western blotting with phospho-specific antibodies. The IC50 value of 4.2 nM is determined by fitting dose-response curves to the inhibition data. The compound is dissolved in DMSO and diluted in assay buffer to achieve the desired final concentrations. Selectivity is assessed by testing the compound against a panel of other kinases. Appropriate positive controls (known MEK inhibitors) and negative controls (DMSO vehicle) are included in each assay run. |
| Cell Assay |
The in vitro cellular assay for Cobimetinib hemifumarate is performed using cancer cell lines that are dependent on the MAPK/ERK pathway for proliferation, such as BRAF-mutant melanoma cell lines. Cells are cultured in appropriate medium and treated with varying concentrations of Cobimetinib hemifumarate or vehicle control (DMSO) for specified time points. Cell viability and proliferation are assessed using assays such as MTT, CellTiter-Glo, or by direct cell counting. ERK1/2 phosphorylation status is assessed by Western blotting using phospho-specific antibodies to confirm target engagement. The compound's effects on downstream signaling and cell cycle progression are evaluated. Dose-response relationships are established by analyzing cell viability and signaling inhibition across different compound concentrations.
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| Animal Protocol |
Female NCR nude mice have had 5 million WM-266-4 melanoma cells intradermally implanted into the hind flank. The cells were resuspended in Hank balanced salt solution. Xenograft mice with tumor volumes of roughly 100 to 120 mm3 are randomly assigned to 4 single dose groups and 4 multiple dose groups on days 11 or 13 following the implantation. Mice in the single dose groups receive a single oral dose of the drug Cobimetinib (GDC-0973, expressed as free base equivalents), vehicle (water for injection USP), 1, 3, or 10 mg/kg one day after randomization and group assignment. For 14 days, mice in the multiple dose groups receive daily oral doses of the GDC-0973 1, 3, or 10 mg/kg, vehicle (water for injection USP), or both. On day 1 (single dose groups) or day 14 (multiple dose groups), plasma and tumor samples (n=3 per time point) are taken from euthanized mice predose and at 2, 4, 8, 16, 24, 72, and 168 hours postdose. Samples are kept until analysis at 80°C. Liquid chromatography/tandem mass spectrometry (LC/MS-MS) is used to assess the concentrations of GDC-0973 in tumor lysates and plasma. The assay's dynamic range is 0.004 to 35 μM.
In vivo animal experiments with Cobimetinib hemifumarate are conducted using immunocompromised mice bearing human BRAF-mutant melanoma xenografts. Tumor cells are implanted subcutaneously into the flank of nude or SCID mice. When tumors reach a predetermined size, animals are randomized into treatment groups receiving Cobimetinib hemifumarate or vehicle control. Cobimetinib is administered orally due to its oral bioavailability. Tumor volume is measured twice weekly using calipers, and body weight is monitored to assess tolerability. At study endpoint, tumors are harvested for analysis of MEK target engagement, ERK phosphorylation, and markers of proliferation and apoptosis. The compound's antitumor efficacy is evaluated by comparing tumor growth in treated versus control groups. Combination studies with vemurafenib are also performed to assess synergistic effects. |
| ADME/Pharmacokinetics |
Detailed pharmacokinetic (PK) parameters for Cobimetinib hemifumarate are available from preclinical and clinical studies. The compound is orally available. Cobimetinib hemifumarate has a molecular weight of 647.38 and a chemical formula of C25H25F3IN3O6 (hemifumarate salt). The compound is soluble in DMSO for formulation purposes. For in vivo oral administration, Cobimetinib is typically formulated using appropriate vehicles to ensure adequate solubility and stability. The compound should be stored under conditions recommended by the manufacturer to maintain stability and prevent degradation. Detailed PK parameters including half-life, clearance, volume of distribution, and maximum concentration (Cmax) are available in the primary literature and should be consulted for specific experimental planning.
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| Toxicity/Toxicokinetics |
Comprehensive toxicological data for Cobimetinib are available from preclinical and clinical studies conducted during its development and FDA approval for melanoma treatment. As a research-grade compound, Cobimetinib hemifumarate is intended for laboratory research purposes only and is not approved for human therapeutic use. Standard laboratory safety practices should be followed when handling this compound. The compound should be stored according to the manufacturer's recommendations to maintain stability and prevent degradation. Toxicological data from preclinical and clinical studies are available in the published literature and should be consulted for safety information.
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| References |
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| Additional Infomation |
Cobimetinib fumarate is a fumarate salt prepared by reacting cobimetinib with one molecule of fumaric acid. It is a mitogen-activated protein kinase inhibitor, used in combination with vemurafenib for the treatment of patients with unresectable or metastatic melanoma. It is an EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor and an antitumor drug. It is a fumarate and an organic ammonium salt. It contains cobimetinib (1+).
See also: Cobimetinib (with active moiety). Drug Indications Cobimetinib is indicated in combination with vemurafenib for the treatment of adult patients with unresectable or metastatic melanoma harboring the BRAF V600 mutation. Cobimetinib hemifumarate is a research compound developed for studying the role of MEK1/2 in the MAPK/ERK signaling pathway and for evaluating MEK inhibition as a therapeutic strategy for cancer. The compound is the hemifumarate salt form of Cobimetinib (GDC-0973), a potent, selective MEK1 inhibitor with an IC50 of 4.2 nM. Cobimetinib was approved by the FDA for the treatment of unresectable or metastatic melanoma with BRAF V600E or V600K mutations, used in combination with vemurafenib. By blocking the activity of MEK1/2, Cobimetinib hemifumarate helps to inhibit tumor cell growth and proliferation. Cobimetinib hemifumarate is available from various chemical suppliers for research purposes. Its utility lies in its ability to inhibit MEK1/2 and probe the role of the MAPK/ERK pathway in cancer. |
| Molecular Formula |
C₂₅H₂₅F₃IN₃O₆
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| Molecular Weight |
647.38
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| Exact Mass |
647.074
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| Elemental Analysis |
C, 46.87; H, 3.93; F, 9.67; I, 21.53; N, 7.13; O, 10.86
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| CAS # |
1369665-02-0
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| Related CAS # |
Cobimetinib;934660-93-2;Cobimetinib racemate;934662-91-6;Cobimetinib (R-enantiomer);934660-94-3
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| PubChem CID |
71491931
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| Appearance |
White to off-white solid powder
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| LogP |
3.832
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| Hydrogen Bond Donor Count |
8
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| Hydrogen Bond Acceptor Count |
18
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
68
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| Complexity |
743
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| Defined Atom Stereocenter Count |
2
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| SMILES |
IC1C=CC(=C(C=1)F)NC1=C(C(=CC=C1C(N1CC(C1)([C@@H]1CCCCN1)O)=O)F)F.IC1C=CC(=C(C=1)F)NC1=C(C(=CC=C1C(N1CC(C1)([C@@H]1CCCCN1)O)=O)F)F.OC(/C=C/C(=O)O)=O
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| InChi Key |
RESIMIUSNACMNW-BXRWSSRYSA-N
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| InChi Code |
InChI=1S/2C21H21F3IN3O2.C4H4O4/c2*22-14-6-5-13(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;5-3(6)1-2-4(7)8/h2*4-7,9,17,26-27,30H,1-3,8,10-11H2;1-2H,(H,5,6)(H,7,8)/b;;2-1+/t2*17-;/m00./s1
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| Chemical Name |
(E)-but-2-enedioic acid;[3,4-difluoro-2-(2-fluoro-4-iodoanilino)phenyl]-[3-hydroxy-3-[(2S)-piperidin-2-yl]azetidin-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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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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 (4.24 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 (4.24 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 (4.24 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: ≥ 2.5 mg/mL (4.24 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 5: ≥ 2.5 mg/mL (4.24 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. 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. Solubility in Formulation 6: 5% DMSO+30% PEG 300+5% Tween 80+ddH2O: 5mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5447 mL | 7.7234 mL | 15.4469 mL | |
| 5 mM | 0.3089 mL | 1.5447 mL | 3.0894 mL | |
| 10 mM | 0.1545 mL | 0.7723 mL | 1.5447 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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