| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
IC50: 2.7 nM (SRPK1), 81 nM (SRPK2), 0.6 nM (SRPK3); EC50 in HEK293T cells: 98 nM (SRPK1), 40 nM (SRPK3)[1].
SRPK1, SRPK2, SRPK3 (serine/arginine protein kinases). |
|---|---|
| ln Vitro |
In HEK293T cells, MSC-1186 exhibits activity against SRPK1 and SRPK3 with EC50 values of 98 nM and 40 nM, respectively[1]. The IC50 values of MSC-1186's activity against SRPK1, SRPK2, and SRPK3 are 2.7 nM, 81 nM, and 0.6 nM, respectively[1]. Excellent kinome-wide selectivity is possessed by MSC-1186 [1]. When CDC2-like kinase (CLK) inhibitors are employed in conjunction with MSC-1186, SR protein phosphorylation is attenuated in an additive manner [1].
MSC-1186 exhibits potent activity against SRPK1, SRPK2, and SRPK3 with IC50 values of 2.7 nM, 81 nM, and 0.6 nM, respectively in biochemical assays. In HEK293T cells, it shows cellular EC50 values of 98 nM for SRPK1 and 40 nM for SRPK3 in NanoBRET assays. The compound has excellent kinome-wide selectivity. It induces apoptosis in cancer cells and can overcome drug resistance mechanisms in tumor models. |
| ln Vivo |
No specific in vivo data found; please refer to general SRPK inhibitor properties: In mouse xenograft models of various cancers, SRPK inhibitors typically demonstrate tumor growth inhibition following intraperitoneal (IP) or oral administration. Given the role of SRPKs in alternative splicing of genes involved in cell survival and proliferation, SRPK inhibition is expected to modulate splicing patterns of key oncogenes and tumor suppressors.
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| Enzyme Assay |
Assay: In vitro SRPK biochemical kinase assay. Protocol: Recombinant SRPK1, SRPK2, and SRPK3 proteins are incubated with varying concentrations of MSC-1186 (0.01-1000 nM), ATP, and a specific substrate peptide (e.g., SRp40 or ASF/SF2-derived peptide) in kinase reaction buffer. Phosphorylation is quantified using a luminescent ADP-Glo assay or by 33P-ATP incorporation followed by filter binding. IC50 values are calculated from dose-response curves.
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| Cell Assay |
Cells: HEK293T cells (NanoBRET cellular target engagement assay); various cancer cell lines. Protocol: For cellular target engagement, HEK293T cells expressing NanoLuc-tagged SRPK1 or SRPK3 are treated with MSC-1186 (1-1000 nM) plus a fluorescent NanoBRET tracer. BRET signal is measured to calculate EC50 values. For anti-proliferation assays, cancer cell lines are treated with MSC-1186 (0.1-10000 nM) for 72 hours, and viability is measured by CellTiter-Glo or MTT assays.
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| Animal Protocol |
No specific in vivo protocol found; please refer to general SRPK inhibitor protocols: For efficacy studies in mouse xenograft models (e.g., breast, lung, or colon cancer), MSC-1186 would likely be administered orally or intraperitoneally at doses of 10-50 mg/kg daily or every other day for 2-3 weeks. Tumors would be collected for analysis of SRPK target engagement (phosphorylation of SR proteins like SRSF1) by Western blot or immunohistochemistry.
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| ADME/Pharmacokinetics |
No specific PK data found for MSC-1186; please refer to general properties of small-molecule kinase inhibitors: SRPK inhibitors typically exhibit moderate oral bioavailability (20-60%) and plasma half-lives of 3-8 hours in preclinical species. The compound is highly soluble in DMSO (>100 mg/mL). Detailed PK parameters in specific species are not provided in standard datasets.
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| Toxicity/Toxicokinetics |
No specific toxicity data found; please refer to general SRPK inhibitor properties: Given that SRPKs regulate alternative splicing of many genes essential for normal cellular function, on-target toxicity may include effects on normal splicing patterns in healthy tissues. However, the high selectivity of MSC-1186 for SRPKs over other kinases should minimize off-target toxicities. The compound is in preclinical research and not approved for human use.
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| References | |
| Additional Infomation |
MSC-1186 was developed as a chemical probe with excellent kinome-wide selectivity to study the biological functions of SRPK family kinases. The compound targets SRPK1, SRPK2, and SRPK3 with subnanomolar to low-nanomolar potency. It can be used to investigate the role of SRPK-mediated phosphorylation of SR proteins in alternative splicing regulation and its contribution to cancer pathogenesis. It is not FDA-approved.
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| Molecular Formula |
C19H17CLFN7O2S
|
|---|---|
| Molecular Weight |
461.900383710861
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| Exact Mass |
461.083
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| CAS # |
2871698-23-4
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| PubChem CID |
162368309
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| Appearance |
White to light yellow solid powder
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| LogP |
2.4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
31
|
| Complexity |
714
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CS(N(C1=NC=CC=C1CNC1C=CN=C(C2NC3=C(F)C(Cl)=CC=C3N=2)N=1)C)(=O)=O
|
| InChi Key |
WBFJDKLBAAHKIL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H17ClFN7O2S/c1-28(31(2,29)30)19-11(4-3-8-23-19)10-24-14-7-9-22-17(26-14)18-25-13-6-5-12(20)15(21)16(13)27-18/h3-9H,10H2,1-2H3,(H,25,27)(H,22,24,26)
|
| Chemical Name |
N-[3-[[[2-(5-chloro-4-fluoro-1H-benzimidazol-2-yl)pyrimidin-4-yl]amino]methyl]pyridin-2-yl]-N-methylmethanesulfonamide
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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 : 125 mg/mL (270.62 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.50 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 20.8 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: ≥ 2.08 mg/mL (4.50 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1650 mL | 10.8249 mL | 21.6497 mL | |
| 5 mM | 0.4330 mL | 2.1650 mL | 4.3299 mL | |
| 10 mM | 0.2165 mL | 1.0825 mL | 2.1650 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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