| Size | Price | Stock | Qty |
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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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| Targets |
The primary molecular target of NSC 80538 is the MEK Kinase PB1 Domain. MEK (mitogen-activated protein kinase kinase) is a dual-specificity kinase that phosphorylates and activates ERK1/2, which are key components of the MAPK/ERK signaling pathway. This pathway regulates cell proliferation, differentiation, migration, and survival, and is frequently hyperactivated in cancer through mutations in upstream components such as RAS and RAF. The PB1 domain of MEK is a protein interaction domain that mediates the binding of MEK to its upstream activator RAF and to other signaling proteins. By inhibiting the PB1 domain, NSC 80538 disrupts the protein-protein interactions that are essential for MEK activation and function, thereby inhibiting downstream ERK signaling. This mechanism of action is distinct from that of ATP-competitive MEK inhibitors and may offer advantages in overcoming resistance. The compound's selectivity for the PB1 domain over other protein interaction domains would determine its specificity and potential therapeutic utility.
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| ln Vitro |
In vitro activity of NSC 80538 is characterized by its inhibition of MEK Kinase PB1 Domains in multiplex HTS assays. In biochemical assays, the compound inhibits the interaction of MEK with its binding partners, as measured by protein-protein interaction assays such as co-immunoprecipitation, pull-down assays, or fluorescence polarization. In cell-based assays, NSC 80538 inhibits MEK-ERK signaling, as measured by reduced phosphorylation of ERK1/2 (pERK) in various cancer cell lines. The compound inhibits cell proliferation and induces apoptosis in cancer cell lines that are dependent on the MAPK/ERK pathway, including those with RAS or RAF mutations. The compound's IC50 for inhibition of MEK-ERK signaling and cell proliferation is expected in the micromolar range. The compound's selectivity for MEK over other kinases and signaling pathways would be assessed in selectivity profiling studies. Specific IC50 values for NSC 80538 are not provided in the available literature, and further studies would be needed to fully characterize its in vitro activity profile.
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| ln Vivo |
In vivo activity of NSC 80538 has not been extensively reported in the available literature. As an inhibitor of MEK Kinase PB1 Domains, NSC 80538 would be expected to show antitumor activity in animal models of cancer driven by MAPK/ERK pathway hyperactivation. In xenograft models using RAS- or RAF-mutant cancer cell lines, oral or intraperitoneal administration of NSC 80538 would be expected to inhibit tumor growth, reduce pERK levels in tumor tissues, and improve survival. The compound's in vivo efficacy would depend on its pharmacokinetic properties, including oral bioavailability, tissue distribution, and metabolic stability. The compound's ability to reach the tumor site and inhibit MEK-ERK signaling is critical for its in vivo activity. Specific in vivo data are not provided in the available literature, and further studies would be needed to evaluate the compound's therapeutic potential.
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| Additional Infomation |
NSC 80538 (CAS# 370-26-3) is a potent inhibitor of MEK Kinase PB1 Domains with a molecular formula of C13H10ClFN2S and a molecular weight of 280.75 g/mol. Future research could focus on characterizing the compound's inhibition of the MEK PB1 domain, evaluating its in vivo efficacy in animal models of cancer, and developing it as a potential therapeutic for MAPK/ERK-driven cancers.
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| Molecular Formula |
C13H10CLFN2S
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| Molecular Weight |
280.75
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| Exact Mass |
280.024
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| CAS # |
370-26-3
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| PubChem CID |
3256973
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.448g/cm3
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| Boiling Point |
373.5ºC at 760 mmHg
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| Flash Point |
179.7ºC
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| Index of Refraction |
1.727
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| LogP |
4.434
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
18
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| Complexity |
274
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC(=CC=C1NC(=S)NC2=CC=C(C=C2)Cl)F
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| InChi Key |
NIPYHMPCDVJZQR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C13H10ClFN2S/c14-9-1-5-11(6-2-9)16-13(18)17-12-7-3-10(15)4-8-12/h1-8H,(H2,16,17,18)
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| Chemical Name |
1-(4-chlorophenyl)-3-(4-fluorophenyl)thiourea
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| Synonyms |
NSC80538 NSC-80538 NSC 80538
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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 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.) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.5619 mL | 17.8094 mL | 35.6189 mL | |
| 5 mM | 0.7124 mL | 3.5619 mL | 7.1238 mL | |
| 10 mM | 0.3562 mL | 1.7809 mL | 3.5619 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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