NU2058

Description: NU2058 (also known as NU 2058; NU-2058; O6-(Cyclohexylmethyl)guanine) is a novel and potent O(6)-Cyclohexylmethylguanine-based CDK2 (cyclin-dependent kinases 2) inhibitor with IC50 of 17 uM in an enzymatic assay. It has potential anticancer activity and can potentiate cisplatin cytotoxicity in vitro. It can also potentiate melphalan (DMF 2.3), and monohydroxymelphalan (1.7), but not temozolomide or ionising radiation. NU2058 increased cisplatin cytotoxicity, by clonogenic assay, with a dose modification factor (DMF) of 3.1. NU2058 increased total intracellular platinum levels 1.5-fold, and platinum-DNA adduct levels twofold. Furthermore, the cisplatin-DNA adducts formed were more toxic in the presence of NU2058. Cellular proliferation is driven by the periodic association of cyclin-dependent kinases (CDKs) and their partner cyclins and controlled by kinase inhibitors, for example p27, and dysregulation of this finely orchestrated process is a characteristic of cancer.

References: Oncogene. 2007 Dec 6; 26(55):7611-9; Biochem Pharmacol. 2009 May 15; 77(10):1586-92.