Description
NU 2058 is an inhibitor of cyclin-dependent kinase 1 (Cdk1) and Cdk2 (IC
50s = 7.0 and 17 μM, respectively). Increased Cdk activity is often associated with human tumors, and inhibitors of Cdks, including NU 2058, can arrest cell cycling in cancer cells
in vitro.
Uses
NU 2058 is an intermediate of NU 6140 (N925295), a cyclin-dependant kinase 2 inhibitor which demonstrates 10-36 fold selectivity against Cdk2-cyclin A. This selectivity induces cell-cycle arrest at the G2-M phase and potentiates the apoptotic effect of pacitaxel.
References
[1] IAN R. HARDCASTLE. N2-Substituted O6-Cyclohexylmethylguanine Derivatives: Potent Inhibitors of Cyclin-Dependent Kinases 1 and 2[J]. Journal of Medicinal Chemistry, 2004, 47 15: 3710-3722. DOI:
10.1021/jm0311442[2] ROGER J. GRIFFIN et al. et al. Structure-Based Design of 2 -Arylamino-4-cyclohexylmethyl-5-nitroso-6-aminopyrimidine Inhibitors of Cyclin-Dependent Kinases 1 and 2.[J]. ChemInform, 2003, 34 51. DOI:
10.1002/chin.200351143[3] N JOHNSON. Pre-clinical evaluation of cyclin-dependent kinase 2 and 1 inhibition in anti-estrogen-sensitive and resistant breast cancer cells[J]. British Journal of Cancer, 2009, 102 2: 342-350. DOI:
10.1038/sj.bjc.6605479[4] A C RIGAS N J C C N Robson. Therapeutic potential of CDK inhibitor NU2058 in androgen-independent prostate cancer[J]. Oncogene, 2007, 26 55: 7611-7619. DOI:
10.1038/sj.onc.1210586
