Home Cell Cycle CDK inhibitor - Aurora Kinase inhibitor JNJ-7706621

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JNJ-7706621 CDK inhibitor

Cat.No.S1249

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 CDK inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 394.36

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Quality Control

Cell Culture, Treatment & Working Concentration

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
HCT116 cells Function assay In vitro inhibitory concentration against cell proliferation in human HCT116 (colon carcinoma) tumor cells, IC50=0.25 μM
human HeLa cells Function assay In vitro inhibitory concentration against cell proliferation in human HeLa (cervical adenocarcinoma) tumor cells, IC50=0.28 μM
human A375 cells Proliferation assay Antiproliferative activity against human A375 cells, IC50=0.447 μM
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
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
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Chemical Information, Storage & Stability

Molecular Weight 394.36 Formula

C15H12F2N6O3S

 Storage (From the date of receipt)
CAS No. 443797-96-4 Download SDF Storage of Stock Solutions

Synonyms N/A Smiles C1=CC(=C(C(=C1)F)C(=O)N2C(=NC(=N2)NC3=CC=C(C=C3)S(=O)(=O)N)N)F

Solubility

In vitro
Batch:

DMSO : 79 mg/mL (200.32 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 3 mg/mL

Water : Insoluble

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo
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In vivo Formulation Calculator (Clear solution)

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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.
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Mechanism of Action

Features
A broad-spectrum inhibitor.
Targets/IC50/Ki
CDK2/CyclinE [1]
(Cell-free assay)
3 nM
CDK2/CyclinA [1]
(Cell-free assay)
4 nM
CDK1/CyclinB [1]
(Cell-free assay)
9 nM
Aurora A [1]
(Cell-free assay)
11 nM
Aurora B [1]
(Cell-free assay)
15 nM
CDK3/CyclinE [1]
(Cell-free assay)
58 nM
VEGFR2 [1]
(Cell-free assay)
154 nM
CDK6/CyclinD1 [1]
(Cell-free assay)
175 nM
FGFR2 [1]
(Cell-free assay)
226 nM
CDK4/CyclinD1 [1]
(Cell-free assay)
253 nM
GSK-3β [1]
(Cell-free assay)
254 nM
Tie-2 [1]
(Cell-free assay)
465 nM
FGFR1 [1]
(Cell-free assay)
575 nM
VEGFR3 [1]
(Cell-free assay)
735 nM
In vitro
JNJ-7706621 also shows some inhibition to VEGF-R2, FGF-R2, and GSK3β, with IC50 of 154-254 nM. This compound 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. It 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, this chemical (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 this compound 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 this compound 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 this chemical 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.
In vivo
In mouse xenograft model of A375 melanoma human tumor, JNJ-7706621 (100 or 125 mg/kg) causes tumor regression. [3]
References

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