JSH-150

Catalog No.S8783

For research use only.

JSH-150 is a highly selective and potent inhibitor of CDK9 with IC50 of 1 nM.

JSH-150 Chemical Structure

CAS No. 2247481-21-4

Purity & Quality Control

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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 Research:

[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 Research:

[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

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)

Chemical Information

Molecular Weight 505.08
Formula

C24H33ClN6O2S

CAS No. 2247481-21-4
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles COCCNC1CCC(CC1)NC2=NC=C(C(=C2)C3=CSC(=N3)NCC4(CCOCC4)C#N)Cl

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

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Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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