Okuyama A, Akiyama T, Nakajima M
Banyu Tsukuba Research Institute, Japan.
Gan To Kagaku Ryoho. 1997 Sep;24(11):1547-62.
CDK inhibitor, Butyrolactone I inhibited CDK1, 2 and 5 in CDKs. In syncronized human lung fibroblast WI38 cells, it inhibited G1/S transition by inhibiting the phosphorylation of RB protein and G2/M transition by inhibiting the phosphorylation of H1 histone. Also, it selectively inhibited the initiation of DNA replication. The MMP inhibitor, BE16627B, reversively inhibited metalloproteinases including MMPs. It showed the MMP-dependent inhibition of the growth and metastasis of human tumor cells in nude mice without any cytotoxicity and severe side effects. The MMP inhibitor, Marimastat, showed remarkable prolongation of the life span of patients with pancreatic tumors in clinical trials.
细胞周期蛋白依赖性激酶（CDK）抑制剂丁内酯I可抑制CDK中的CDK1、2和5。在同步化的人肺成纤维细胞WI38中，它通过抑制RB蛋白的磷酸化来抑制G1/S期转换，并通过抑制H1组蛋白的磷酸化来抑制G2/M期转换。此外，它还能选择性地抑制DNA复制的起始。基质金属蛋白酶（MMP）抑制剂BE16627B可逆转抑制包括MMPs在内的金属蛋白酶。它在裸鼠中表现出对人肿瘤细胞生长和转移的MMP依赖性抑制作用，且无任何细胞毒性和严重副作用。MMP抑制剂马立马司他在临床试验中显著延长了胰腺癌患者的生存期。
