JNJ-7706621Potent CDK/Aurora kinase inhibitor CAS# 443797-96-4 |
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Quality Control & MSDS
3D structure
Package In Stock
Number of papers citing our products
| Cas No. | 443797-96-4 | SDF | Download SDF |
| PubChem ID | 5330790 | Appearance | Powder |
| Formula | C15H12F2N6O3S | M.Wt | 394.36 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO : ≥ 125 mg/mL (316.97 mM) *"≥" means soluble, but saturation unknown. | ||
| Chemical Name | 4-[[5-amino-1-(2,6-difluorobenzoyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide | ||
| SMILES | C1=CC(=C(C(=C1)F)C(=O)N2C(=NC(=N2)NC3=CC=C(C=C3)S(=O)(=O)N)N)F | ||
| Standard InChIKey | KDKUVYLMPJIGKA-UHFFFAOYSA-N | ||
| Standard InChI | InChI=1S/C15H12F2N6O3S/c16-10-2-1-3-11(17)12(10)13(24)23-14(18)21-15(22-23)20-8-4-6-9(7-5-8)27(19,25)26/h1-7H,(H2,19,25,26)(H3,18,20,21,22) | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | JNJ-7706621 is a potent inhibitor of cyclin-dependent kinases (CDK) and Aurora kinases with IC50 values of 9 nM, 4 nM, 11 nM and 15 nM for CDK1, 2 and Aurora A, B, respectively. | ||||||
| Targets | CDK1 | CDK2 | Aurora A | Aurora B | |||
| IC50 | 9 nM | 4 nM | 11 nM | 15 nM | |||
JNJ-7706621 Dilution Calculator
JNJ-7706621 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 2.5358 mL | 12.6788 mL | 25.3575 mL | 50.7151 mL | 63.3939 mL |
| 5 mM | 0.5072 mL | 2.5358 mL | 5.0715 mL | 10.143 mL | 12.6788 mL |
| 10 mM | 0.2536 mL | 1.2679 mL | 2.5358 mL | 5.0715 mL | 6.3394 mL |
| 50 mM | 0.0507 mL | 0.2536 mL | 0.5072 mL | 1.0143 mL | 1.2679 mL |
| 100 mM | 0.0254 mL | 0.1268 mL | 0.2536 mL | 0.5072 mL | 0.6339 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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JNJ-7706621 is a dual inhibitor of cyclin-dependent kinases (CDK) and Aurora kinases that potently inhibits CDK1, CDK2, CDK3, CDK4, CDK6, Aurora-A, and Aurora-B in vitro with 50% inhibition concentration IC50 values of 0.009, 0.004, 0.003, 0.058, 0.253, 0.175, 0.011 and 0.015 μmol/L respectively. JNJ-7706621 selectively inhibits proliferation of both normal human cells and tumor cells of various origins, where the efficacy of JNJ-7706621 is 10-fold greater in tumor cells (IC50 range of 0.112 to 0.514 μmol/L) than normal cells (IC50 range of 3.67 to 5.42 μmol/L). JNJ-7706621 has been found to induce apoptosis, suppress colony formation and inhibit cell growth regardless of p53, retinoblastoma or P-glycoprotein status in human cancer cells.
Reference
Stuart Emanuel, Catherine A. Rugg, Robert H. Gruninger, Ronghui Lin, Angel Fuentes-Pesquera, Peter J. Connolly, Steven K. Wetter, Beth Hollister, Walter W. Kruger, Cheryl Napier, Linda Jolliffe, and Steven A. Middleton. The In vitro and In vivo Effects of JNJ-7706621: A Dual Inhibitor of Cyclin-Dependent Kinases and Aurora Kinases. Cancer Res 2005;65:9038-9046
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Synthesis and evaluation of N-acyl sulfonamides as potential prodrugs of cyclin-dependent kinase inhibitor JNJ-7706621.[Pubmed:16682186]
Bioorg Med Chem Lett. 2006 Jul 15;16(14):3639-41.
A novel prodrug strategy for cyclin-dependent kinase inhibitor JNJ-7706621 has been explored. Through N-acylation of a sulfonamide substituent, tails containing different solubilizing groups (amino, carboxyl, alkoxyl, and hydroxyl) were attached to JNJ-7706621. Most of the prodrugs exhibited good aqueous solubility and the N-acyl groups on the sulfonamide were metabolically cleaved to generate active drug in rat PK study.
The in vitro and in vivo effects of JNJ-7706621: a dual inhibitor of cyclin-dependent kinases and aurora kinases.[Pubmed:16204078]
Cancer Res. 2005 Oct 1;65(19):9038-46.
Modulation of aberrant cell cycle regulation is a potential therapeutic strategy applicable to a wide range of tumor types. JNJ-7706621 is a novel cell cycle inhibitor that showed potent inhibition of several cyclin-dependent kinases (CDK) and Aurora kinases and selectively blocked proliferation of tumor cells of various origins but was about 10-fold less effective at inhibiting normal human cell growth in vitro. In human cancer cells, treatment with JNJ-7706621 inhibited cell growth independent of p53, retinoblastoma, or P-glycoprotein status; activated apoptosis; and reduced colony formation. At low concentrations, JNJ-7706621 slowed the growth of cells and at higher concentrations induced cytotoxicity. Inhibition of CDK1 kinase activity, altered CDK1 phosphorylation status, and interference with downstream substrates such as retinoblastoma were also shown in human tumor cells following drug treatment. Flow cytometric analysis of DNA content showed that JNJ-7706621 delayed progression through G1 and arrested the cell cycle at the G2-M phase. Additional cellular effects due to inhibition of Aurora kinases included endoreduplication and inhibition of histone H3 phosphorylation. In a human tumor xenograft model, several intermittent dosing schedules were identified that produced significant antitumor activity. There was a direct correlation between total cumulative dose given and antitumor effect regardless of the dosing schedule. These results show the therapeutic potential of this novel cell cycle inhibitor and support clinical evaluation of JNJ-7706621.
Active and passive tumor targeting of a novel poorly soluble cyclin dependent kinase inhibitor, JNJ-7706621.[Pubmed:20226846]
Int J Pharm. 2010 Jun 15;392(1-2):20-8.
The anti-cancer cyclin dependent kinase (CDK) inhibitors are poorly soluble drugs. The aims of this work were (i) to formulate a novel CDK inhibitor, JNJ-7706621, in polymeric micelles and nanoparticles, (ii) to compare passive and active targeting on tumor growth and (iii) to evaluate the potential synergy of JNJ-7706621 with Paclitaxel. Therefore, JNJ-7706621 was encapsulated in self-assembling diblock copolymers made up of epsilon-caprolactone (CL) and trimethylene carbonate (TMC) (PEG-p-(CL-co-TMC)) polymeric micelles and in (poly(lactide-co-glycolide)) (PLGA)-based PEGylated nanoparticles (passive targeting) as well as in RGD-grafted nanoparticles (active targeting). In vivo, the transplantable liver tumor growth was more decreased by active targeting with RGD-grafted nanoparticles than by passive targeting with micelles or ungrafted nanoparticles. Moreover, a synergy between JNJ-7706621 and Paclitaxel was demonstrated. Therefore, active targeting of JNJ-7706621-loaded nanocarriers may be considered as an effective anti-cancer drug delivery system for cancer chemotherapy, particularly in combination with Paclitaxel.
Growth suppression and mitotic defect induced by JNJ-7706621, an inhibitor of cyclin-dependent kinases and aurora kinases.[Pubmed:22463590]
Curr Cancer Drug Targets. 2012 Jul;12(6):625-39.
Aurora kinases and cyclin-dependent kinases, which play critical roles in the cell cycle and are frequently overexpressed in a variety of tumors, have been suggested as attractive targets for cancer therapy. JNJ-7706621, a recently identified dual inhibitor of these kinases, is reported to induce cell cycle arrest, endoreduplication, and apoptosis. In the present study, we further investigated the molecular mechanisms underlying these effects. The inhibitor arrested various cells at G2 phase at low concentration, and at both G1 and G2 phases at high concentration. JNJ-7706621 did not prevent localization of Aurora A to the spindle poles, but did inhibit other centrosomal proteins such as TOG, Nek2, and TACC3 in early mitotic phase. Similarly, the drug did not prevent localization of Aurora B to the kinetochore, but did inhibit other chromosomal passenger proteins such as Survivin and INCENP. In the cells exposed to JNJ-7706621 after nocodazole release, Aurora B, INCENP, and Survivin became relocated to the peripheral region of chromosomes, but Plk1 and Prc1 were localized on microtubules in later mitotic phase. Treatment of nocodazole-synchronized cells with JNJ-7706621 was able to override mitotic arrest by preventing spindle checkpoint signaling, resulting in failure of chromosome alignment and segregation. Injection of the drug significantly inhibited the growth of TC135 Ewing's sarcoma cells transplanted into athymic mice by cell cycle arrest and apoptosis. JNJ-7706621 is a unique inhibitor regulating cell cycle progression at multiple points, suggesting that it could be useful for cell cycle analysis and therapy of various cancers, including Ewing's sarcoma.
