| Size | Price | Stock | Qty |
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| 5mg |
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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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| Other Sizes |
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SLV-2436 is a highly potent and ATP-competitive inhibitor of MNK1 and MNK2 with IC50s of 10.8 nM and 5.4 nM, respectively.
| Targets |
MNK2 (IC50 = 5.4 nM); MNK1 (IC50 = 10.8 nM)
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|---|---|
| ln Vitro |
The broad KINOMEscan competitive binding assay, which includes 450 different kinases, is carried out at 1 M to verify SLV-2436's (SEL201's) kinome selectivity. MNK1 and MNK2 are part of the CAMK family of kinases, which accounts for a significant portion of the observed binding profile for SLV-2436. Reduced oncogenicity and reduced capacity for metastasis are observed in KIT-mutant melanoma cells treated with SLV-2436[1].
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| ln Vivo |
Mice are given 5 consecutive oral doses of 10, 25, and 50 mg/kg every 12 hours (twice daily schedule) to test the pharmacodynamic effects of SLV-2436 (SEL201). A low plasma concentration of 125 ng/mL SLV-2436 is found at the 10 mg/kg twice-daily dosage 4 hours after the fifth administration. However, doses of 50 and 100 mg/kg/d of SLV-2436, or 25 and 50 mg/kg twice daily, result in significantly increased dose-dependent plasma exposure, with average levels of 1,299 ng/mL and 2,075 ng/mL, respectively. SLV-2436 is still detectable in the plasma at the 24-hour mark, with dose-dependent concentrations of 9, 73, and 124 ng/mL in the 10, 25, and 50 mg/kg twice-daily treatment groups, respectively. Mice respond well to oral (p.o.) administration of SLV-2436 at a dosage of 50 mg/kg twice daily, or 100 mg/kg/d, for 37 days[1].
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| Cell Assay |
In 6-well plates, 1,000 HBL, MM61, MM111, and M230 cell lines are seeded per well and allowed to adhere for the night. Following an overnight incubation, the cells are given either DMSO (control) or SLV-2436 (5 μM) treatment. The media are taken out of the wells after 14 days, and the cells are stained with 0.5% (wt/vol) crystal violet in 70% ethanol. After the staining dye has been washed off after an hour at room temperature, the colony counts are calculated using GelCount. The test is carried out in three duplicates[1].
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| Animal Protocol |
Mice: The pharmacokinetic profile of SLV-2436 is evaluated in female CD-1 mice that are 6 weeks old. Freshly dissolved SLV-2436 is administered in DMSO and Captisol at a volume of 10 μL per 1 g of body weight for oral (5 mg/kg) or intravenous (2 mg/kg) administration. At each of the eight time points—5, 15, and 30 minutes; 1, 2, 4, 6, and 24 hours—animals are sacrificed, and blood is taken. For further analysis, plasma samples are collected and kept at -80°C. 10- to 16-week-old male C57BL/6 mice are divided into a control group and 3 dosing groups to assess the pharmacodynamic properties of SLV-2436. Animals are given freshly dissolved 10-, 25-, and 50-mg/kg doses of either the vehicle (DMSO+N,N-Dimethylacetamide+Captisol) or SLV-2436. 10 μL of medication are injected intravenously for every 1 g of body weight. On a twice-daily schedule (i.e., every 12 hours), each animal received a total of 5 doses. Each day, the body weight is calculated. Three animals were used for sample collection at each of the two time points (i.e., 4 hours and 24 hours) following the final, fifth administration when there were six animals per experimental group. In preparation for additional analysis, plasma samples are collected and kept at -80°C[1].
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| References |
| Molecular Formula |
C19H15CLN4O
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|---|---|
| Molecular Weight |
350.801602602005
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| Exact Mass |
350.09
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| Elemental Analysis |
C, 65.05; H, 4.31; Cl, 10.11; N, 15.97; O, 4.56
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| CAS # |
2095704-43-9
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| Related CAS # |
2095704-43-9
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| PubChem CID |
129052025
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| Appearance |
Light brown to brown solid powder
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| LogP |
3
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
25
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| Complexity |
578
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
YQVUADHJKWJHAF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H15ClN4O/c20-15-3-1-2-12(8-15)10-24-11-14(5-7-18(24)25)13-4-6-16-17(9-13)22-23-19(16)21/h1-9,11H,10H2,(H3,21,22,23)
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| Chemical Name |
5-(3-amino-1H-indazol-6-yl)-1-[(3-chlorophenyl)methyl]pyridin-2-one
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| Synonyms |
SLV-2436; SLV2436; SLV 2436; SEL-201-88; SEL201-88; SEL 201-88; SEL 201; SEL-201; SEL201
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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: ~70 mg/mL (~199.5 mM)
Ethanol: ~5 mg/mL (~14.3 mM) |
|---|---|
| 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 | 2.8506 mL | 14.2531 mL | 28.5063 mL | |
| 5 mM | 0.5701 mL | 2.8506 mL | 5.7013 mL | |
| 10 mM | 0.2851 mL | 1.4253 mL | 2.8506 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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