1. Cell Cycle/DNA Damage
    Epigenetics
  2. Aurora Kinase
    CDK

JNJ-7706621 

Cat. No.: HY-10329 Purity: 99.82%
Data Sheet SDS Handling Instructions

JNJ-7706621 is a potent aurora kinase inhibitor, and also inhibits CDK1 and CDK2, with IC50s of 9, 3, 11, and 15 nM for CDK1, CDK2, Aurora-A and Aurora-B, respectively.

For research use only. We do not sell to patients.
JNJ-7706621 Chemical Structure

JNJ-7706621 Chemical Structure

CAS No. : 443797-96-4

Size Price Stock Quantity
10 mM * 1 mL in DMSO $121 In-stock
2 mg $80 In-stock
5 mg $140 In-stock
10 mg $250 In-stock
50 mg $610 In-stock
100 mg $1170 In-stock
200 mg   Get quote  
500 mg   Get quote  

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  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

JNJ-7706621 is a potent aurora kinase inhibitor, and also inhibits CDK1 and CDK2, with IC50s of 9, 3, 11, and 15 nM for CDK1, CDK2, Aurora-A and Aurora-B, respectively.

IC50 & Target

IC50: 3 nM (CDK2), 9 nM (CDK1), 11 nM (Aurora-A), 15 nM (Aurora-B)[4]

In Vitro

JNJ-7706621 shows antiproliferative activity against various human tumor cells with IC50s of 284, 254, and 447 nM for HeLa, HCT116, and A375, respectively[1]. JNJ-7706621 inhibits other centrosomal proteins such as TOG, Nek2, and TACC3 in early mitotic phase, but does not prevent localization of Aurora A to the spindle poles. Treatment of nocodazole-synchronized cells with JNJ-7706621 can override mitotic arrest by preventing spindle checkpoint signaling, resulting in failure of chromosome alignment and segregation[2]. JNJ-7706621 suspensions inhibits cell viability of HeLa cells with IC50s of 2.1 and 0.9 μg/mL at 24 and 48 h. The IC50 of the JNJ-7706621-loaded nanoparticles are 35 and 2.7 μg/mL and the IC50 of the JNJ-7706621-loaded micelles are 6.3 and 1.6 μg/mL[3]. JNJ-7706621 shows inhibition of Aurora-A and Aurora-B but has no activity at the highest concentration tested on the Plk1 or Wee1 serine/threonine kinases. JNJ-7706621 also shows potent growth inhibition in vitro on all human cancer cell types with IC50 values ranging from 112 to 514 nM[4].

In Vivo

JNJ-7706621 (100 mg/kg, i.p.) exhibits 95% tumor growth inhibition in A375 (human melanoma) tumor xenograft model[1]. JNJ-7706621-loaded micelles inhibit tumor growth, and delay the tumor growth more efficiently than the control JNJ-7706621 suspension[3]. JNJ-7706621 (100 and 125 mg/kg) is efficacious in a human tumor xenograft model under intermittent dosing regimens[4].

References
Preparing Stock Solutions
Concentration Volume Mass 1 mg 5 mg 10 mg
1 mM 2.5358 mL 12.6788 mL 25.3575 mL
5 mM 0.5072 mL 2.5358 mL 5.0715 mL
10 mM 0.2536 mL 1.2679 mL 2.5358 mL
Please refer to the solubility information to select the appropriate solvent.
Kinase Assay
[4]

To identify compounds that inhibit CDK1 kinase activity, a screening method is developed using the CDK1/cyclin B complex to phosphorylate a biotinylated peptide substrate containing the consensus phosphorylation site for histone H1, which is phosphorylatedin vivo by CDK1. Inhibition of CDK1 activity is measured by observing a reduced amount of 33P-g-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 Na3VO4, 1 mM DTT, 1% DMSO, 0.25 AM peptide, 0.1 ACi per well 33P-g-ATP (2,000-3,000 Ci/mmol), and 5 AM ATP in the presence or absence of various concentrations of test 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 test compound is used to determine IC50 values. The Aurora kinase assays are done with 10 AM ATP and a peptide containing a dual repeat of the kemptide phosphorylation motif. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay
[3]

HeLa cells are seeded in 96-well plates at the density of 2500 viable cells per well. The cells are then incubated with a suspension of JNJ-7706621, JNJ-7706621-loaded micelles and nanoparticles (JNJ-7706621 concentrations of 0.011, 0.022, 0.11, 0.22, 1.1, 2.2, 11 and 22 μg/mL; dilutions are made in the medium) and drug-free polymeric micelles (polymers concentrations 0.3 mg/mL) and nanoparticles (polymers concentration 5 mg/mL) for 4, 24 and 48 h. The cytotoxicity is assessed using the MTT test. Absorbance is measured at 570 nm using a microplate reader. Untreated cells are taken as control with 100% viability and Triton X-100 1% is used as positive control of cytotoxicity. The results are expressed as mean values ± standard deviations of five measurements. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[4]

JNJ-7706621 formulated as a nanocrystal suspension in 1.5% pluronic acid F108.

Briefly, animals are implanted s.c. with 1 mm3 A375 tumor fragments in the hindflank. After tumors reach 62 to 126 mg, groups are pair matched. Animals are given JNJ-7706621 or vehicle control starting on day 1. The tumor growth delay method is followed where each animal is euthanized when its neoplasm reached a predetermined size of 2.0 g. All statistical analyses are conducted using unpaired t tests at a P level of 0.05 (two tailed). MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

394.36

Formula

C₁₅H₁₂F₂N₆O₃S

CAS No.

443797-96-4

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

10 mM in DMSO

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

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