JNJ-7706621 - CAS 443797-96-4
Catalog number: 443797-96-4
Category: Inhibitor
Please be kindly noted products are not for therapeutic use. We do not sell to patients.
Molecular Formula:
C15H12F2N6O3S
Molecular Weight:
394.36
COA:
Inquire
Targets:
Aurora Kinase
Description:
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.
Synonyms:
JNJ-7706621; JNJ-7706621; JNJ-7706621
MSDS:
Inquire
InChIKey:
KDKUVYLMPJIGKA-UHFFFAOYSA-N
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)
Canonical SMILES:
C1=CC(=C(C(=C1)F)C(=O)N2C(=NC(=N2)NC3=CC=C(C=C3)S(=O)(=O)N)N)F
Current Developer:
Johnson; Johnson Pharmaceutical Research; Development,
1.Synthesis and evaluation of N-acyl sulfonamides as potential prodrugs of cyclin-dependent kinase inhibitor JNJ-7706621.
Huang S1, Connolly PJ, Lin R, Emanuel S, Middleton SA. Bioorg Med Chem Lett. 2006 Jul 15;16(14):3639-41. Epub 2006 May 6.
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.
2.Active and passive tumor targeting of a novel poorly soluble cyclin dependent kinase inhibitor, JNJ-7706621.
Danhier F1, Ucakar B, Magotteaux N, Brewster ME, Préat V. Int J Pharm. 2010 Jun 15;392(1-2):20-8. doi: 10.1016/j.ijpharm.2010.03.018. Epub 2010 Mar 11.
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.
3.Growth suppression and mitotic defect induced by JNJ-7706621, an inhibitor of cyclin-dependent kinases and aurora kinases.
Matsuhashi A1, Ohno T, Kimura M, Hara A, Saio M, Nagano A, Kawai G, Saitou M, Takigami I, Yamada K, Okano Y, Shimizu K. 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.
Molecular Weight Calculator Molarity Calculator Solution Dilution Calculator

Related Aurora Kinase Products


CAS 827318-97-8 Danusertib

Danusertib
(CAS: 827318-97-8)

Danusertib is a small-molecule 3-aminopyrazole derivative with potential antineoplastic activity. Aurora kinase inhibitor PHA-739358 binds to and inhibits the A...

CAS 885325-71-3 MK-8745

MK-8745
(CAS: 885325-71-3)

MK-8745 is a novel Aurora-A specific inhibitor. MK8745 induced apoptotic cell death in a p53-dependent manner when tested in vitro in cell lines of multiple lin...

CAS 422513-13-1 Hesperadin

Hesperadin
(CAS: 422513-13-1)

Hesperadin is  an inhibitor of human Aurora B, which can prevent the phosphorylation of substrate with IC(50) of 40 nM. Growth of cultured bloodstream forms was...

CAS 722543-31-9 Barasertib

Barasertib
(CAS: 722543-31-9)

Barasertib is an orally bioavailable, small-molecule, dihydrogen phosphate prodrug of the pyrazoloquinazoline Aurora kinase inhibitor AZD1152–hydroxyquinazolin...

CAS 898280-07-4 XL228

XL228
(CAS: 898280-07-4)

XL228 is a protein kinase inhibitor targeting IGF1R, the Aurora kinases, FGFR1-3, ABL and SRC family kinases.

CAS 1158838-43-7 Aurora A inhibitor II

Aurora A inhibitor II
(CAS: 1158838-43-7)

Aurora A inhibitor II is a potent and selective inhibitor of Aurora A kinase (AurA; IC50 = 4.3 nM).

CAS 934353-76-1 ENMD-2076

ENMD-2076
(CAS: 934353-76-1)

ENMD-2076 is an orally-active, Aurora A/angiogenic kinase inhibitor with a unique kinase selectivity profile and multiple mechanisms of action. ENMD-2076 has be...

CAS 639089-54-6 Tozasertib

Tozasertib
(CAS: 639089-54-6)

The Aurora kinases (A, B, and C) are a family of serine-threonine kinases that regulate various stages of mitotic function. With significant roles in cell cycle...

Chemical Structure

CAS 443797-96-4 JNJ-7706621

Quick Inquiry

Verification code

Featured Items