摘要
蛋白酶体是存在于所有真核细胞中的多功能催化蛋白酶 ,是细胞蛋白质降解通路中最主要的组成部分 ,是许多细胞调节信号的中心通道 ,因而成为药物治疗的新目标。PS 341是蛋白酶体有效的选择性抑制药。在体外和小鼠异基因移植的研究中 ,PS 341表现了抗多种肿瘤的活性 ,包括骨髓瘤、慢性淋巴细胞白血病 (CLL)、前列腺癌、胰腺癌、结肠癌等。药效学分析表明蛋白酶体抑制药的抑制作用有剂量依赖性和可逆性。Ⅰ期临床试验中 ,PS 341在治疗多种肿瘤时表现了较好耐受性。治疗难治性多发性骨髓瘤、CLL和实体瘤的Ⅱ期临床试验正在进行 ,并已取得初步结果。
The proteasome is a multicatalytic protease that presents in all eukaryotic cells, is the primary component of the protein degradation pathway of the cell. By degrading regulatory proteins, the proteasome serves as a central channel for many cellular regulatory singnals and is a novel target for drug therapy. PS 341 is a potent and selective inhibitor of the proteasome. In vitro and mouse xenograft studies, PS 341 has shown antitumor activity in a variety of types, including myeloma, chronic lymphocytic leukemia, prostate cancer, pancreatic cancer, and colon cancer etc. Pharmacodynamic assay has shown that inhibition of proteasome is dose dependent and reversible. In phase I trials of a variety of tumor types, PS 341 has shown that it is well tolerated. Phase Ⅱ trials in several hematologic malignancies and solid tumor types are now in progress and have got some achievements. Phase Ⅲ trials will begin soon.
出处
《中国新药与临床杂志》
CAS
CSCD
北大核心
2003年第9期550-553,共4页
Chinese Journal of New Drugs and Clinical Remedies
