| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
MEK1[1]
MEK1, MEK2 |
|---|---|
| ln Vitro |
Nedometinib is a selective MEK1/2 inhibitor with a biochemical IC₅0 of 135 nM for MEK1. It inhibits the growth of human squamous cell lines in a dose‑dependent manner, and suppresses MAPK pathway signaling in the skin. It is metabolically labile, designed for rapid local clearance to minimize systemic exposure.
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| ln Vivo |
In vivo, topical application of nedometinib gel demonstrates localized MEK1/2 inhibition in the skin, leading to reduced MAPK pathway activity in cutaneous lesions. The metabolically labile nature of the compound ensures rapid clearance from systemic circulation, minimizing off‑target effects. It has been evaluated in animal models of neurofibromatosis and cutaneous tumors.
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| Enzyme Assay |
For biochemical IC₅0 determination, recombinant MEK1/2 proteins are incubated with nedometinib (0.1‑1000 nM) in the presence of ATP, and kinase activity is measured using a coupled assay. For topical gel formulation studies, in vitro skin penetration is assessed using Franz diffusion cells with human or porcine skin.
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| Cell Assay |
Cells (e.g., human squamous cell lines) are treated with nedometinib (1 nM - 10 uM) for 24‑72 h. Cell viability is measured by MTT or CellTiter-Glo assays, and MAPK pathway inhibition is confirmed by Western blotting for phospho‑ERK. For topical formulation studies, skin tissue homogenates are also analyzed for MEK1/2 activity.
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| Animal Protocol |
Nedometinib gel (0.5‑5%) is applied topically once or twice daily to the skin of mice bearing cutaneous lesions or subcutaneous xenografts. Drug concentrations in skin and plasma are measured at multiple time points to assess local exposure and systemic leakage. PD endpoints include phospho‑ERK levels in skin biopsies.
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| ADME/Pharmacokinetics |
No detailed PK data for nedometinib has been reported. However, as a metabolically labile inhibitor designed for topical administration, it is expected to have low systemic absorption, rapid local clearance, and minimal systemic exposure, thereby reducing the risk of class‑related toxicities associated with oral MEK inhibitors.
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| Toxicity/Toxicokinetics |
No detailed toxicity data for nedometinib has been reported. The compound is designed to be metabolically labile, which is expected to reduce systemic toxicity by promoting rapid clearance from circulation. Topical application may cause local skin irritation at high concentrations, but no systemic toxicity has been reported.
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| References | |
| Additional Infomation |
Nedometinib is a topical gel formulation composed of mitogen-activated protein kinase inhibitors (MAP2K; MAPKK; MEK) with potential antitumor activity. After topical application, Nedometinib penetrates the dermis, specifically targeting and binding to MEK, inhibiting its catalytic activity, thereby suppressing the activation of MEK-dependent effector proteins (including extracellular signal-regulated kinases (ERKs)) and inhibiting tumor cell proliferation due to overactivation of the RAS/RAF/MEK/ERK signaling pathway. Threonine/tyrosine protein kinase MEK plays a crucial role in the RAS/RAF/MEK/ERK signaling pathway, which is frequently upregulated in various tumor cell types and regulates key cellular activities including cell growth, proliferation, survival, differentiation, and apoptosis. NFX-179 degrades rapidly after entering systemic circulation, minimizing side effects from systemic exposure.
Nedometinib (NFX‑179; CAS: 2252314-46-6; formula: C1₇H1₆FIN4O3; MW: 470.2) is a novel MEK1/2 inhibitor in preclinical/early clinical development for dermatological indications. Its topical formulation and metabolic lability are unique among MEK inhibitors, enabling localized efficacy for conditions like cutaneous neurofibromas. No FDA approval or published clinical trial results have been reported. |
| Molecular Formula |
C17H16FIN4O3
|
|---|---|
| Molecular Weight |
470.236819267273
|
| Exact Mass |
470.025
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| CAS # |
2252314-46-6
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| PubChem CID |
146585168
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
3.1
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| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
26
|
| Complexity |
489
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
IC1C=CC(=C(C=1)F)NC1=C(C(NOCCO)=O)C2=CC=CN=C2N1C
|
| InChi Key |
SENAOZROGSYRTD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H16FIN4O3/c1-23-15-11(3-2-6-20-15)14(17(25)22-26-8-7-24)16(23)21-13-5-4-10(19)9-12(13)18/h2-6,9,21,24H,7-8H2,1H3,(H,22,25)
|
| Chemical Name |
2-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)-1-methylpyrrolo[2,3-b]pyridine-3-carboxamide
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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: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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: 100 mg/mL (212.66 mM)
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1266 mL | 10.6329 mL | 21.2657 mL | |
| 5 mM | 0.4253 mL | 2.1266 mL | 4.2531 mL | |
| 10 mM | 0.2127 mL | 1.0633 mL | 2.1266 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.
Link: https://clinicaltrials.gov/ct2/show/NCT05005845
Conditions:Cutaneous Neurofibroma|Neurofibromatosis 1Link: https://clinicaltrials.gov/ct2/show/NCT04435665
Conditions:Neurofibromatosis 1|Cutaneous NeurofibromaProducts are for research use only; We do not sell to patients
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