Home Cell Cycle CDK inhibitor - Aurora Kinase inhibitor JNJ-7706621 For research use only.

JNJ-7706621

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.

JNJ-7706621 Chemical Structure

JNJ-7706621 Chemical Structure

CAS No. 443797-96-4

Purity & Quality Control

JNJ-7706621 Related Products

Signaling Pathway

CDK Signaling Pathways

CDK Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
PC3 cells Function assay In vitro inhibitory concentration against cell proliferation in human PC-3 (prostate adenocarcinoma) tumor cells, IC50=0.12 μM 15974571
HCT116 cells Function assay In vitro inhibitory concentration against cell proliferation in human HCT116 (colon carcinoma) tumor cells, IC50=0.25 μM 15974571
human HeLa cells Function assay In vitro inhibitory concentration against cell proliferation in human HeLa (cervical adenocarcinoma) tumor cells, IC50=0.28 μM 15974571
human A375 cells Proliferation assay Antiproliferative activity against human A375 cells, IC50=0.447 μM 16682186
MDA-MB-231 cells Function assay In vitro inhibitory concentration against cell proliferation in various human MDA-MB-231 (breast carcinoma) tumor cells, IC50=0.59 μM 15974571
SK-OV-3 cells Function assay In vitro inhibitory concentration against cell proliferation in human SK-OV-3 (ovarian adenocarcinoma) tumor cells, IC50=0.75 μM 15974571
Click to View More Cell Line Experimental Data

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.
Features A broad-spectrum inhibitor.
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)		 Click to View More Targets
3 nM 4 nM 9 nM 11 nM 15 nM
In vitro
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]
Kinase Assay 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 Research 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.
In Vivo
In vivo In mouse xenograft model of A375 melanoma human tumor, JNJ-7706621 (100 or 125 mg/kg) causes tumor regression. [3]
Animal Research Animal Models Mouse xenograft model of A375 cells
Dosages 100 or 125 mg/kg
Administration Orally or by intraperitoneal injection injection

Chemical Information & Solubility

Molecular Weight 394.36 Formula

C15H12F2N6O3S
CAS No. 443797-96-4 SDF Download JNJ-7706621 SDF
Smiles C1=CC(=C(C(=C1)F)C(=O)N2C(=NC(=N2)NC3=CC=C(C=C3)S(=O)(=O)N)N)F
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 79 mg/mL ( (200.32 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 3 mg/mL

Water : Insoluble


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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.

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