JNJ-7706621 (JNJ7706621) is novel and potent pan-CDK (cyclin-dependent kinases) inhibitor and also an Aurora-A and Aurora-B inhibitor with potential antitumor activity. It inhibits CDK1/2 with IC50 of 9 nM/4 nM and exhibits >6-fold selectivity for CDK1/2 over CDK3/4/6 in cell-free assays. It also potently inhibits Aurora A/B and has little/no activity on Plk1 and Wee1. It shows potent in vitro antiproliferative activity and high in vivo antitumor efficacy.

Physicochemical Properties

Molecular Formula	C15H12F2N6O3S
Molecular Weight	394.36
Exact Mass	394.065
CAS #	443797-96-4
Related CAS #	443797-96-4
PubChem CID	5330790
Appearance	White to off-white solid powder
Density	1.7±0.1 g/cm3
Boiling Point	676.6±65.0 °C at 760 mmHg
Melting Point	149-155ºC
Flash Point	363.0±34.3 °C
Vapour Pressure	0.0±2.1 mmHg at 25°C
Index of Refraction	1.724
LogP	0.18
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	4
Heavy Atom Count	27
Complexity	630
Defined Atom Stereocenter Count	0
InChi Key	KDKUVYLMPJIGKA-UHFFFAOYSA-N
InChi Code	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)
Chemical Name	4-((5-amino-1-(2,6-difluorobenzoyl)-1H-1,2,4-triazol-3-yl)amino)benzenesulfonamide
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	The anti-proliferative activity of JNJ-7706621 has been seen against a range of human tumor cells, including HeLa, HCT116, and A375, with IC50 values of 284, 254, and 447 nM, respectively [1]. During early mitosis, JNJ-7706621 inhibits TOG, Nek2, and TACC3, among other centrosomal proteins, but it does not stop Aurora A from localizing to spindle poles. By inhibiting spindle checkpoint signaling, JNJ-7706621 treatment of nocodazole-synchronized cells can prevent mitotic arrest and prevent chromosomal alignment and segregation failure [2]. When tested against Plk1 or Wee1 serine/threonine kinases at the highest concentrations, JNJ-7706621 was inactive but inhibited Aurora-A and Aurora-B. With IC50 values ranging from 112 to 514 nM, JNJ-7706621 exhibited strong growth inhibition against all human cancer cell types in vitro [3]. HeLa cell viability is inhibited by JNJ-7706621 suspension, with IC50 values of 2.1 and 0.9 μg/mL at 24 and 48 hours, respectively. The JNJ-7706621-loaded nanoparticles had an IC50 of 35 and 2.7 μg/mL, respectively, while the micelles had an IC50 of 6.3 and 1.6 μg/mL, respectively [4].
ln Vivo	In human tumor xenograft models, JNJ-7706621 (100 and 125 mg/kg) works well when administered intermittently [3]. In an A375 (human melanoma) tumor xenograft model, JNJ-7706621 (100 mg/kg, i.p.) showed 95% tumor growth inhibition [1]. More successfully than the control group, JNJ-7706621 suspension postponed tumor growth, and JNJ-7706621 loaded micelles inhibited tumor growth [4].
Animal Protocol	Dissolved in 0.5% methylcellulose containing 0.1% polysorbate 80 in sterile water; 100, 125 mg/kg; oral administration or i.p. injection. Mouse xenograft model of A375 cells
References	[1]. Synthesis and evaluation of N-acyl sulfonamides as potential prodrugs of cyclin-dependent kinase inhibitor JNJ-7706621. Bioorg Med Chem Lett. 2006 Jul 15;16(14):3639-41. Epub 2006 May 6. [2]. Growth suppression and mitotic defect induced by JNJ-7706621, an inhibitor of cyclin-dependent kinases and aurora kinases. Curr Cancer Drug Targets. 2012 Jul;12(6):625-39. [3]. The in vitro and in vivo effects of JNJ-7706621: a dual inhibitor of cyclin-dependent kinases and aurora kinases. Cancer Res. 2005 Oct 1;65(19):9038-46. [4]. Active and passive tumor targeting of a novel poorly soluble cyclin dependent kinase inhibitor, JNJ-7706621. Int J Pharm. 2010 Jun 15;392(1-2):20-8.
Additional Infomation	4-[[5-amino-1-[(2,6-difluorophenyl)-oxomethyl]-1,2,4-triazol-3-yl]amino]benzenesulfonamide is a sulfonamide.

Solubility Data

Solubility (In Vitro)

DMSO: 79 mg/mL (200.3 mM) Water:<1 mg/mL Ethanol:<1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.27 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.27 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 3: 0.5% methylcellulose+0.2% Tween 80:14mg/mL  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		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

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.