CGP 60474

CGP 60474 is an inhibitor of cyclin-dependent kinases (CDKs; IC₅₀s = 0.017, 0.08, and 0.05 µM for Cdk1/cyclin B, Cdk2/cyclin A, and Cdk2/cyclin E, respectively).¹ It is selective for these CDKs over Cdk4/cyclin D1 (IC₅₀ = 0.7 µM) and a variety of other kinases, including several PKC isoforms (IC₅₀s = 1.9->100 µM), PKA (IC₅₀ = 160 µM), and FLT1 (IC₅₀ = 1 µM), among others, but does inhibit PKCα and v-Abl (IC₅₀s = 0.25 and 0.4 µM, respectively). It inhibits proliferation of colon, breast, lung, prostate, and ovarian cancer cells (IC₅₀s = 25-84, 21-280, 40 and 68, 17 and 20, and 18-38 nM, respectively). CGP 60474 also reduces LPS-induced IL-6, TNF-α, and RANTES secretion from J774.1 cells in a concentration-dependent manner and inhibits poly(I:C)-induced NF-κB nuclear translocation in the same cells when used at concentrations of 8 and 32 nM.² It reduces plasma IL-6 levels and increases survival in a mouse model of LPS-induced endotoxemia when administered at a dose of 10 mg/kg.

WARNING This product is not for human or veterinary use.

1. Ruetz, S., Fabbro, D., Zimmermann, J., et al. Chemical and biological profile of dual Cdk1 and Cdk2 inhibitors. Curr. Med. Chem. Anticancer Agents 3(1), 1-14 (2003).

2. Han, H.-W., Hahn, S., Jeong, H.Y., et al. LINCS L1000 dataset-based repositioning of CGP-60474 as a highly potent anti-endotoxemic agent. Sci. Rep. 8(1), 14969 (2018).