P276 化学特性,用途語,生産方法
使用
P276-00 is a cyclin-dependent kinase (CDK) inhibitor. P276-00 has shown to be highly selective for cancer cells and has shown to produce potent inhibition of Cdk4-D1 activity. P276-00 also induces apoptosis in human promyelocytic leukemia (HL-60) cells.
酵素阻害剤
This cell cycle-inhibiting flavone and anticancer agent (FW = 438.30 g/mol; CAS 920113-03-7), also named 2-(2-chlorophenyl)-5,7-dihydroxy-8- [(2R,3S)-2-(hydroxymethyl)-1-methyl-3-pyrrolidinyl]-4H-1-benzopyran-4- one, targets the Cyclin-Dependent Kinases CDK1 (IC50 = 79 nM), CDK4 (IC50 = 63 nM) and CDK9 (IC50 = 20 nM). p276-00 showed potent antiproliferative effects against various human cancer cell lines (IC50 values ranging from 300 to 800 nmol/L), but has little effect on cultured fibroblasts. A significant down-regulation of cyclin D1 and Cdk4 and a decrease in Cdk4-specific pRb Ser(780) phosphorylation is observed. P276-00 produces potent inhibition of Cdk4-D1 activity that is competitive with ATP, and not with retinoblastoma protein. The compound also induced apoptosis in human promyelocytic leukemia (HL-60) cells, as evidenced by the induction of caspase-3 and DNA ladder studies. In 22 human cancer xenografts, P276-00 is approximately 26x more potent than cisplatin, and is also active against cisplatin-resistant tumors of central nervous system, melanoma, prostate, and renal cancers. Synchronized human non-small cell lung carcinoma (H-460) and human normal lung fibroblast (WI-38) cells are arrested in G1
P276 上流と下流の製品情報
原材料
920112-99-8
920113-01-5
cis-((2S,3R)-1-methyl-3-(2,4,6-trimethoxyphenyl)pyrrolidin-2-yl)methanol
((2R,3S)-1-methyl-3-(2,4,6-trimethoxyphenyl)pyrrolidin-2-yl)methanol
1,2,3,6-TETRAHYDRO-1-METHYL-4-(2,4,6-TRIMETHOXYPHENYL)-PYRIDINE
P276-00 (free base)
2-クロロベンゾイルクロリド
2-クロロ安息香酸
1,3,5-トリメトキシベンゼン
準備製品