NU6102 is a novel and potent inhibitor of Cdk1 and Cdk2 with Kis of 9 and 6 nM and IC50 of 9.5 and 5.4 nM, respectively. NU 6102 inhibits Cdk4 activity with an IC50 of 1.6 μM
Physicochemical Properties
| Molecular Formula | C18H22N6O3S |
| Molecular Weight | 402.47068 |
| Exact Mass | 402.147 |
| CAS # | 444722-95-6 |
| PubChem CID | 4566 |
| Appearance | White to yellow solid powder |
| Density | 1.6±0.1 g/cm3 |
| Boiling Point | 612.9±65.0 °C at 760 mmHg |
| Flash Point | 324.5±34.3 °C |
| Vapour Pressure | 0.0±1.8 mmHg at 25°C |
| Index of Refraction | 1.746 |
| LogP | 1.42 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 28 |
| Complexity | 601 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | OWXORKPNCHJYOF-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C18H22N6O3S/c19-28(25,26)14-8-6-13(7-9-14)22-18-23-16-15(20-11-21-16)17(24-18)27-10-12-4-2-1-3-5-12/h6-9,11-12H,1-5,10H2,(H2,19,25,26)(H2,20,21,22,23,24) |
| Chemical Name | 4-((6-(cyclohexylmethoxy)-9H-purin-2-yl)amino)benzenesulfonamide |
| Synonyms | NU6102 NU-6102 NU 6102. |
| 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 | NU6102 selectively inhibits the growth of CDK2 WT (wild type) and KO MEF (knockout mouse embryonic fibroblasts) (GI50 of 14 μM and >30 μM). Treatment with NU6102 (0-30 μM; 1-24 hours; SKUT 1B cells) induces G2 arrest, inhibition of Rb phosphorylation, and cytotoxicity in SKUT-1B cells (LC50 after 24 hours of exposure is 2.6 μM) [3]. NU6102 inhibits cell growth and causes cell cycle phase arrest in a time-dependent manner in human breast cancer cell lines, G2/M phase arrest in asynchronously growing cell lines, cells released by serum starvation, and G1 in the nucleus of Xenopus laevis cells /S phase arrest[3]. |
| ln Vivo | After administering NU6102 intravenously and intraperitoneally to Balb/C mice, the drug's pharmacokinetics were ascertained. The maximum dosing dose of NU6102 is 1 mg/kg iv and 10 mg/kg ip due to its limited solubility. NU6301 releases NU6102 after ip or iv administration, and peak plasma levels of 12 μM NU6102 are observed 5 minutes after iv administration. The peak concentration reached after intravenous injection of the maximum dose of NU6102 was 0.92 μM. Following the injection of NU6301, the plasma half-life of NU6102 is 42 minutes for intraperitoneal administration and 10 minutes for intravenous administration [3]. |
| Cell Assay |
Cell cycle analysis[3] Cell Types: SKUT 1B Cell Tested Concentrations: 0 μM, 3 μM, 10 μM and 30 μM Incubation Duration: 1 hour, 3 hrs (hours), 6 hrs (hours) and 24 hrs (hours) Experimental Results: Induction of G2 arrest, inhibition of Rb phosphorylation and cytotoxicity (LC50 2.6 μM after 24 hrs (hours) of exposure). |
| References |
[1]. N2-substituted O6-cyclohexylmethylguanine derivatives: potent inhibitors of cyclin-dependent kinases 1 and 2. J Med Chem. 2004 Jul 15;47(15):3710-22. [2]. Dissecting the determinants of cyclin-dependent kinase 2 and cyclin-dependent kinase 4 inhibitor selectivity. J Med Chem. 2006 Sep 7;49(18):5470-7. [3]. Preclinical in vitro and in vivo evaluation of the potent and specific cyclin-dependent kinase 2 inhibitor NU6102 and a water soluble prodrug NU6301. Eur J Cancer. 2011 Sep;47(13):2052-9. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~100 mg/mL (~248.47 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.21 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 25.0 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: ≥ 2.5 mg/mL (6.21 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (6.21 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4847 mL | 12.4233 mL | 24.8466 mL | |
| 5 mM | 0.4969 mL | 2.4847 mL | 4.9693 mL | |
| 10 mM | 0.2485 mL | 1.2423 mL | 2.4847 mL |