生物活性

• 描述The protein kinase C (PKC) family is a group of cytosolic serine/threonine kinases that play crucial roles in cell proliferation, differentiation, and cellular signal transductions. The cyclin dependent kinases (CDK) are a family of enzymes involved in cell cycle regulation and oncogenesis. CGP-60474 is a disubstituted pyrimidine-pyridine that inhibits both PKC and CDK^[3]. It inhibits CDK1/cyclinB, CDK2/cyclinA, CDK2/cyclinE, PKC-α, and v-Abl with IC50 values of 17, 80, 50, 250, and 400 nM, respectively. The anti-proliferative effect of CGP-60474 was observed in a panel of tumor cell lines, including colon cancer cells (DLD-1, HTC-15, HTC-116, Colo 205), breast cancer cells (MDA-MB-453, MDA-MB-231, MDA-MB-468, BT-20, ZR-75-1, MCF-7), lung cancer cells (A549, NCI-H596), prostate cancer cells (DU-145, PC-3), ovary cancer cells (PA-1, SW-626, ES-2) with IC50 values ranging from 17 - 280 nM. The treatment of osteosarcoma cell lines U2OS and U2OS/Tag with increasing doses of CGP60474 resulted in a time-dependent growth arrest with IC50 values of 95 and 115 nM, respectively. In normal human fibroblast cell line WI-38, CGP60474 treatment also inhibited the phosphorylation of pRB, a known downstream target of CDK2^[4].
• 作用机制CGP-60474 is a CDK inhibitor that docks to the ATP-binding site region of CDK2^[5].