| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
Purity: =98.85%
| Targets |
Gamcemetinib targets MK2 (MAPKAPK2), a serine/threonine protein kinase that is a downstream effector of the p38 MAP kinase pathway. MK2 plays a critical role in the regulation of inflammatory responses, cell migration, and proliferation. By covalently and irreversibly binding to MK2, gamcemetinib inhibits its kinase activity, thereby blocking the downstream signaling pathways that contribute to inflammation and disease progression.
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| ln Vitro |
In biochemical (IC50=156.3 nM) and cell-based studies (EC50 = 89 nM), gamcemetinib is a strong, covalent, irreversible activator of mitogen-activated protein (MAP)-activated mitogen-activated protein-2 (MK2)[1].
In vitro, gamcemetinib is a potent inhibitor of MK2. It has a biochemical IC50 of 156.3 nM and a cellular EC50 of 89 nM. Its covalent and irreversible mechanism of action provides sustained inhibition of the target. The compound's potency in both biochemical and cell-based assays confirms its activity as an MK2 inhibitor. |
| ln Vivo |
In vivo, gamcemetinib has been evaluated in clinical trials for various indications. It has a maximum clinical trial phase of II (across all indications). As an investigational drug, it is being studied for its potential to treat inflammatory and oncological conditions. Specific in vivo efficacy data, including dosing regimens and animal models, would be detailed in the primary literature and clinical trial reports.
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| Enzyme Assay |
The inhibitory activity of gamcemetinib is assessed using in vitro kinase assays. Recombinant MK2 enzyme is incubated with a peptide substrate and varying concentrations of the compound in the presence of ATP. The IC50, the concentration required to inhibit 50% of kinase activity, is calculated from the dose-response curve. Its covalent and irreversible mechanism is confirmed by assessing the time-dependence of inhibition or by using washout experiments.
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| Cell Assay |
The cellular activity of gamcemetinib is evaluated in cell lines relevant to MK2 biology. Cells are treated with the compound, and its effect on MK2 activity is assessed by measuring the phosphorylation of MK2 substrates, such as heat shock protein 27 (HSP27). The EC50, the concentration required for 50% of the maximal effect in cells, is determined. The compound's effect on cell viability, cytokine production, and migration can also be assessed.
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| Animal Protocol |
In animal studies, gamcemetinib is typically administered orally or via intraperitoneal injection. In models of inflammation, its effect on disease severity and inflammatory markers is assessed. In oncology models, its effect on tumor growth and metastasis is evaluated. Dosing regimens are determined based on its pharmacokinetic properties. Pharmacodynamic markers, such as the phosphorylation of HSP27, are measured to confirm target engagement.
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| ADME/Pharmacokinetics |
Gamcemetinib has a molecular weight of 469.95 g/mol and a chemical formula of C25H27ClF3N5O2. It is soluble in DMSO (94 mg/mL) and is typically stored as a powder at -20°C. It is an investigational drug that has been evaluated in clinical trials, with a maximum phase of II. Detailed pharmacokinetic parameters are available from preclinical and clinical studies.
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| Toxicity/Toxicokinetics |
The toxicity profile of gamcemetinib is being evaluated in clinical trials. As an MK2 inhibitor, its safety profile would be characterized by its mechanism of action and potential off-target effects. Common adverse events and dose-limiting toxicities would be identified in ongoing studies. Its safety is being monitored in clinical trials for various indications.
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| References | |
| Additional Infomation |
Gamcemetinib (CC-99677, CAS: 1887069-10-4) is a potent, covalent, and irreversible MK2 inhibitor that has been advanced to clinical trials. It is also known as BMS-986371. Its mechanism of action involves the irreversible inhibition of the p38 MAPK downstream effector MK2, making it a valuable tool for studying inflammatory and oncological pathways. Its development highlights the therapeutic potential of targeting the MK2 pathway.
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| Molecular Formula |
C22H20CLN5O3S
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|---|---|
| Molecular Weight |
469.94
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| Exact Mass |
469.097
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| CAS # |
1887069-10-4
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| Related CAS # |
1887069-10-4;
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| PubChem CID |
118936948
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.5
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
32
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| Complexity |
678
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| Defined Atom Stereocenter Count |
1
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| SMILES |
N1[C@@H](CNC2C3=C(C=CC4=NC(OC5C(COCC)=CN=C(Cl)N=5)=CC=C34)SC=2C1=O)C
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| InChi Key |
PYOQIOLRFIRRSO-LLVKDONJSA-N
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| InChi Code |
InChI=1S/C22H20ClN5O3S/c1-3-30-10-12-9-25-22(23)28-21(12)31-16-7-4-13-14(27-16)5-6-15-17(13)18-19(32-15)20(29)26-11(2)8-24-18/h4-7,9,11,24H,3,8,10H2,1-2H3,(H,26,29)/t11-/m1/s1
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| Chemical Name |
(15R)-5-[2-chloro-5-(ethoxymethyl)pyrimidin-4-yl]oxy-15-methyl-11-thia-6,14,17-triazatetracyclo[8.8.0.02,7.012,18]octadeca-1(10),2(7),3,5,8,12(18)-hexaen-13-one
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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 |
| 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) |
DMSO : ~37.5 mg/mL (~79.80 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 1.5 mg/mL (3.19 mM) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 15.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 + to the above solution and mix evenly; then add 450 μL of 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1279 mL | 10.6397 mL | 21.2793 mL | |
| 5 mM | 0.4256 mL | 2.1279 mL | 4.2559 mL | |
| 10 mM | 0.2128 mL | 1.0640 mL | 2.1279 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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