JSH-150

Catalog No.S8783 Batch:S878301

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Technical Data

Formula

C24H33ClN6O2S
Molecular Weight 505.08 CAS No. 2247481-21-4
Solubility (25°C)* In vitro DMSO 100 mg/mL (197.98 mM)
Water 100 mg/mL (197.98 mM)
Ethanol 100 mg/mL (197.98 mM)
In vivo (Add solvents to the product individually and in order)
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
5.0mg/ml Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
Clear solution
5% DMSO 95% Corn oil
0.83mg/ml Taking the 1 mL working solution as an example, add 50 μL of 16.6 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description JSH-150 is a highly selective and potent inhibitor of CDK9 with IC50 of 1 nM.
Targets
CDK9 [1]
(Cell-free assay)
1 nM
In vitro

JSH-150 exhibits an IC50 of 1 nM against CDK9 kinase in the biochemical assay and achieves around 300-10000-fold selectivity over other CDK kinase family members. In addition, it also displays high selectivity over other 468 kinases/mutants. JSH-150 displays potent antiproliferative effects against melanoma, neuroblastoma, hepatoma, colon cancer, lung cancer as well as leukemia cell lines. It can dose-dependently inhibit the phosphorylation of RNA Pol II, suppress the expression of MCL-1 and C-Myc, arrest the cell cycle and induce the apoptosis in the leukemia cells.[1]
In vivo

In the MV4-11 cell-inoculated xenograft mouse model, 10 mg/kg dosage of JSH-150 can almost completely suppress the tumor progression. The high selectivity and good in vivo PK/PD profile suggests that JSH-150 will be a good pharmacological tool to study CDK9-mediated physiology and pathology as well as a potential drug candidate for leukemia and other cancers.[1]

Protocol (from reference)

Kinase Assay:

[1]
  • The ADP-Glo kinase assay

    The kinase reaction system contains 4.5 μL of CDK9/CyclinK kinase (3 ng/μL), 0.5 μL of serially diluted compounds 11-43 (including JSH-150), and 5 μL of CDK9 substrate PDKtide (0.2 μg/μL) with 10 μM ATP. The reaction in each tube is started immediately by adding ATP and keeps going for an hour under 37 °C. After the tube is cooled for 5 min at room temperature, 5 μL solvent reactions are carried out in a 384-well plate. Then 5 μL of ADP-Glo reagent is added into each well to stop the reaction and consume the remaining ADP within 40 min. At the end, 10 μL of kinase detection reagent is added into the well and incubated for 30 min to produce a luminescence signal. Luminescence signal is measured with an automated plate reader and the dose−response curve is fitted using Prism 7.0.
Cell Assay:

[1]
  • Cell lines

    MV4-11, HL-60 and MEC-1 cells

  • Concentrations

    serially diluted/various concentrations

  • Incubation Time

    2 h

  • Method

    Signaling Pathway Study. MV4-11, HL-60 and MEC-1 cells are treated with DMSO, serially diluted JSH-150, 1 μM compound 7 for 2 h. Cells are then washed in 1 × PBS and lysed in cell lysis buffer. Phospho-CDK9 (Thr186), CDK9, Phospho-RNA Pol II (Ser2), Phospho-RNA Pol II (Ser5), RNA Pol II, XIAP, MCL-1, C-MYC, BCL-2 and GAPDH antibody are used for immunoblotting.
Animal Study:

[1]
  • Animal Models

    Female nu/nu mice, Sprague-Dawley rats and beagle dogs

  • Dosages

    3 mg/kg, 10 mg/kg, 20 mg/kg, 2 mg/kg

  • Administration

    IV, Oral gavage

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.