BS-181 HCl

Catalog No.S1572 Batch:S157202

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Technical Data

Formula

C22H32N6.HCl
Molecular Weight 416.99 CAS No. 1397219-81-6 
Solubility (25°C)* In vitro DMSO 83 mg/mL (199.04 mM)
Water 83 mg/mL (199.04 mM)
Ethanol 22 mg/mL (52.75 mM)
* <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.)

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Biological Activity

Description BS-181 HCl is a highly selective CDK7 inhibitor with IC50 of 21 nM. It is more than 40-fold selective for CDK7 than CDK1, 2, 4, 5, 6, or 9.
Targets
CDK7 [1]
(Cell-free assay)
21 nM
In vitro BS-181 is a small molecule inhibitor of CDK7 in a cell-free environment, which displays more potential activity than roscovitine with IC 50 of 510 nM. Among the CDKs and other 69 kinases from many different classes, BS-181 shows high inhibitory selectivity for CDK7, inhibits CDK2 at concentrations lower than 1 μM which being inhibited 35-fold less potently (IC50 with 880 nM) than CDK7, shows slight inhibition for CDK1, CDK4, CDK5, CDK6 and CDK9 with IC50 values higher than 3.0 μM, and only shows inhibition for several kinases from other classes at high concentrations (>10 μM). BS-181 promotes cell cycle arrest and inhibits the cancer cell growth of a range of tumor types, including breast, lung, prostate and colorectal cancer with IC50 in the range of 11.5-37 μM. In MCF-7 cells, BS-181 inhibits the phosphorylation of the CDK7 substrate RNA polymerase II COOH-terminal domain (CTD), and promotes cell cycle arrest and apoptosis to inhibit the growth of cancer cell lines. [1]
In vivo BS-181 is stable in vivo with a plasma elimination half-life in mice of 405 minutes after i.p. administration of 10 mg/kg. BS-181 inhibits the growth of MCF-7 xenografts in the nude mice model in a dose-dependent manner, with 25% and 50% reduction in tumor growth after 2 weeks of treatment at 10 mg/kg/day and 20 mg/kg/day, respectively without apparent toxicity. [1]
Features Demonstrates higher inhibitory selectivity for CDK7 vs. other CDKs and kinases from other classes.

Protocol (from reference)

Kinase Assay:[1]
  • In vitro kinase inhibition.

    Inhibition of CDK7 activity is measured by incubation of increasing amounts of BS-181 with purified recombinant CDK7/CycH/MAT1 complex, followed by measurement of free ATP remaining in the reaction using a luciferase assay, luciferase activity therefore providing a measure of inhibition of CDK7 activity for the determination of IC50.
Cell Assay:[1]
  • Cell lines

    MCF-7 cells

  • Concentrations

    Dissolved in DMSO, final concentration ~50 μM

  • Incubation Time

    24 hours

  • Method

    MCF-7 cells are exposed to BS-181 for 24 hours. For the determination of cell cycle and apoptosis, cells are stained with propidium iodide or labeled with Annexin V-FITC, then labeled cells are acquired within 1 hour, by using the RXP cytomics software on a Beckman Coulter Elite ESP, and the data are analyzed using Flow Jo v7.2.5. For the assessment of CDKs, cells are lysed and analyzed by western blotting.
Animal Study:[1]
  • Animal Models

    MCF-7 cells are established in female nu/nu-BALB/c athymic nude mice

  • Dosages

    10 or 20 mg/kg

  • Administration

    Twice daily by i.p. injection

Customer Product Validation

, , Dr. Vladimir Krystof of Palacky University

Data from [Data independently produced by , , Mol Cancer Ther, 2016, 15(7):1495-503]

Data from [Data independently produced by , , Oncotarget, 2016, 7(36):58051-58064]

Data from [Data independently produced by , , Reprod Biol, 2017, 1.446]

Selleck's BS-181 HCl has been cited by 16 publications

Inhibition of CDK7-dependent transcriptional addiction is a potential therapeutic target in synovial sarcoma [ Biomed Pharmacother, 2022, 149:112888] PubMed: 35367753
G1 Cell Cycle Arrest and Extrinsic Apoptotic Mechanisms Underlying the Anti-Leukemic Activity of CDK7 Inhibitor BS-181 [ Cancers (Basel), 2020, 12(12)E3845] PubMed: 33352782
G1 Cell Cycle Arrest and Extrinsic Apoptotic Mechanisms Underlying the Anti-Leukemic Activity of CDK7 Inhibitor BS-181 [ Cancers (Basel), 2020, 12(12)3845] PubMed: 33352782
MYC up-regulation confers resistance to everolimus and establishes vulnerability to cyclin dependent kinase inhibitors in pancreatic neuroendocrine neoplasms cells [ Neuroendocrinology, 2020, 10.1159/000509865] PubMed: 32615570
A simple high-throughput approach identifies actionable drug sensitivities in patient-derived tumor organoids. [ Commun Biol, 2019, 2:78] PubMed: 30820473
Coordination between TGF-β cellular signaling and epigenetic regulation during epithelial to mesenchymal transition [ Epigenetics Chromatin, 2019, 12(1):11] PubMed: 30736855
How Selective Are Pharmacological Inhibitors of Cell-Cycle-Regulating Cyclin-Dependent Kinases? [ J Med Chem, 2018, 61(20):9105-9120] PubMed: 30234987
ERβ inhibits cyclin dependent kinases 1 and 7 in triple negative breast cancer [ Oncotarget, 2017, 8(57):96506-96521] PubMed: 29228549
Effects of CDK inhibitors on the maturation, transcription, and MPF activity of porcine oocytes [Oqani RK, et al. Reprod Biol, 2017, 17(4):320-326] PubMed: 28935119
HOXC10 expression supports the development of chemotherapy resistance by fine tuning DNA repair in breast cancer cells [Sadik H, et al. Cancer Res, 2016, 10.1158/0008-5472.CAN-16-0774] PubMed: 27302171

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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.

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