CGP60474

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 CDK³. 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 CDK2⁴.

溶解方案(细胞实验)

DMSO 中的溶解度 : ≥ 50 mg/mL (140.52 mM; 吸湿的 DMSO 对产品的溶解度有显著影响，请使用新开封的 DMSO)|* "≥" means soluble, but saturation unknown.

溶解方案(动物实验)

"方案 一": "请依序添加每种溶剂：10% DMSO 40% PEG300 5% Tween-80 45% SalineSolubility: ≥ 2.5 mg/mL (7.03 mM); 澄清溶液 此方案可获得 ≥ 2.5 mg/mL（饱和度未知）的澄清溶液。以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；再向上述体系中加入 50 μL Tween-80，混合均匀；然后再继续加入 450 μL 生理盐水 定容至 1 mL。生理盐水的配制：将 0.9 g 氯化钠，溶解于 ddH₂O 并定容至 100 mL，可以得到澄清透明的生理盐水溶液。"

"方案 二": "请依序添加每种溶剂：10% DMSO 90% Corn OilSolubility: ≥ 2.5 mg/mL (7.03 mM); 澄清溶液 此方案可获得 ≥ 2.5 mg/mL（饱和度未知）的澄清溶液，此方案实验周期在半个月以上的动物实验酌情使用。以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。"