JNJ-7706621

Catalog No.S1249 Batch:S124902

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Technical Data

Formula

C15H12F2N6O3S
Molecular Weight 394.36 CAS No. 443797-96-4
Solubility (25°C)* In vitro DMSO 79 mg/mL (200.32 mM)
Water Insoluble
Ethanol Insoluble
* <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 JNJ-7706621 is a pan-CDK inhibitor with the highest potency on CDK1/2 with IC50 of 9 nM/4 nM and showing >6-fold selectivity for CDK1/2 than CDK3/4/6 in cell-free assays. It also potently inhibits Aurora A/B and has no activity on Plk1 and Wee1.
Targets
CDK2/CyclinE [1]
(Cell-free assay)		 CDK2/CyclinA [1]
(Cell-free assay)		 CDK1/CyclinB [1]
(Cell-free assay)		 Aurora A [1]
(Cell-free assay)		 Aurora B [1]
(Cell-free assay)		 View More
3 nM 4 nM 9 nM 11 nM 15 nM
In vitro JNJ-7706621 also shows some inhibition to VEGF-R2, FGF-R2, and GSK3β, with IC50 of 154-254 nM. JNJ-7706621 shows inhibitory effect on a panel of human cancer cell types, including HeLa, HCT-116, SK-OV-3, PC3, DU145, A375, MDA-MB-231, MES-SA, and MES-SA/Dx5, with IC50 of 112-514 nM, independent of p53, retinoblastoma, or P-glycoprotein status. JNJ-7706621 is several-fold less potent at inhibiting growth of normal cell types, including MRC-5, HASMC, HUVEC, and HMVEC, with IC50 of 3.67-5.42 μM. In HeLa or U937 cells, JNJ-7706621 (0.5-3 μM) delays exit from G1, arrests cells in G2-M, induces endoreduplication, activates apoptosis, and reduces colony formation. [1] In a HeLa cell line, incremental treatment with increasing concentrations of JNJ-7706621 leads to a 16-fold resistance, which may be mediated by ABCG2. [2]
In vivo In mouse xenograft model of A375 melanoma human tumor, JNJ-7706621 (100 or 125 mg/kg) causes tumor regression. [3]
Features A broad-spectrum inhibitor.

Protocol (from reference)

Kinase Assay:[1]
  • In vitro kinase assay for CDK1 and Aurora kinases

    For CDK1 kinase activity, a method is developed using the CDK1/cyclin B complex purified from baculovirus to phosphorylate a biotinylated peptide substrate containing the consensus phosphorylation site for histone H1, which is phosphorylated in vivo by CDK1. Inhibition of CDK1 activity is measured by observing a reduced amount of 33P-γ-ATP incorporation into the immobilized substrate in streptavidin-coated 96-well scintillating microplates. CDK1 enzyme is diluted in 50 mM Tris-HCl (pH 8), 10 mM MgCl2, 0.1 mM Na3VO 4, 1 mM DTT, 1% DMSO, 0.25 μM peptide, 0.1 μCi per well 33P-γ-ATP, and 5 μM ATP in the presence or absence of various concentrations of JNJ-7706621 and incubated at 30 °C for 1 hour. The reaction is terminated by washing with PBS containing 100 mM EDTA and plates are counted in a scintillation counter. Linear regression analysis of the percent inhibition by JNJ-7706621 is used to determine IC50. The Aurora kinase assays are done with 10 μM ATP and a peptide containing a dual repeat of the kemptide phosphorylation motif.
Cell Assay:[3]
  • Cell lines

    HeLa, HCT-116, A375, SK-OV-3, MDA-MB-231, and PC-3 cells

  • Concentrations

    1 nM - 10 μM, dissolved in DMSO

  • Incubation Time

    48 hours

  • Method

    The ability of JNJ-7706621 to inhibit the proliferation of cell growth is determined by measuring incorporation of 14C-labelled thymidine into newly synthesized DNA within the cells. Cells are trypsinized and counted and 3-8 × 103 cells are added to each well of a 96-well CytoStar tissue culture treated scintillating microplate in complete medium in a volume of 100 μL. Cells are incubated for 24 hours in complete medium at 37 °C in an atmosphere containing 5% CO2. Next, 1 μL of JNJ-7706621 is added to the wells of the plate. Cells are incubated for 24 more hours. Methyl 14C-thymidine 56 mCi/mmol is diluted in complete medium and 0.2 μCi/well is added to each well of the CytoStar plate in a volume of 20 μL. The plate is incubated for 24 hours at 37 °C in JNJ-7706621 plus 14C-thymidine. The contents of the plate are discarded and the plate is washed twice with 200 μL PBS. 200 μL of PBS is added to each well. The top of the plate is sealed with a transparent plate sealer and a white plate backing sealer is applied to the bottom of the plate. The degree of methyl 14C-thymidine incorporation is quantified on a Packard Top Count.
Animal Study:[1]
  • Animal Models

    Mouse xenograft model of A375 cells

  • Dosages

    100 or 125 mg/kg

  • Administration

    Orally or by intraperitoneal injection injection

Customer Product Validation

Data from [Data independently produced by Oncogene, 2014, 10.1038/onc.2014.351]

Data from [Data independently produced by Mol Cancer Ther, 2014, 13(3), 662-74]

, , Dr. Zhang of Tianjin Medical University

, , Dr. Yong-Weon Yi from Georgetown University Medical Center

Selleck's JNJ-7706621 has been cited by 25 publications

Inhibitors of One or More Cellular Aurora Kinases Impair the Replication of Herpes Simplex Virus 1 and Other DNA and RNA Viruses with Diverse Genomes and Life Cycles [ Microbiol Spectr, 2023, 11(1):e0194322] PubMed: 36537798
Integrative analysis of drug response and clinical outcome in acute myeloid leukemia [ Cancer Cell, 2022, S1535-6108(22)00312-9] PubMed: 35868306
Nascent transcriptome reveals orchestration of zygotic genome activation in early embryogenesis [ Curr Biol, 2022, 32(19):4314-4324.e7] PubMed: 36007528
Inhibition of IκB Kinase Is a Potential Therapeutic Strategy to Circumvent Resistance to Epidermal Growth Factor Receptor Inhibition in Triple-Negative Breast Cancer Cells [ Cancers (Basel), 2022, 14(21)5215] PubMed: 36358633
Dual Inhibition of AKT and MEK Pathways Potentiates the Anti-Cancer Effect of Gefitinib in Triple-Negative Breast Cancer Cells [ Cancers (Basel), 2021, 13(6)1205] PubMed: 33801977
Transcriptome Analysis and Functional Identification of Adipose-Derived Mesenchymal Stem Cells in Secondary Lymphedema [ Gland Surg, 2020, 9(2):558-574] PubMed: 32420291
The TRAPP complex mediates secretion arrest induced by stress granule assembly. [ EMBO J, 2019, 38(19):e101704] PubMed: 31429971
DRUGPATH - a novel bioinformatic approach identifies DNA-damage pathway as a regulator of size maintenance in human ESCs and iPSCs [ Sci Rep, 2019, 9(1):1897] PubMed: 30760778
CDK9 modulates circadian clock by attenuating REV-ERBα activity. [ Biochem Biophys Res Commun, 2019, 513(4):967-973] PubMed: 31005255
Targeted Polo-like Kinase Inhibition Combined With Aurora Kinase Inhibition in Pediatric Acute Leukemia Cells. [ J Pediatr Hematol Oncol, 2019, 41(6):e359-e370] PubMed: 30702467

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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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