Isoform-specific inhibitors of ACATs: recent advances and promising developments.
Isoform-specific inhibitors of ACATs: recent advances and promising developments.
复制标题
ACAT 异构体特异性抑制剂：最新进展和有希望的发展。
作者：
Taichi Ohshiro;H. Tomoda
酰基辅酶A：胆固醇酰基转移酶（ACAT）是心血管疾病的一个有前途的治疗靶点。尽管已经开发了许多合成的ACAT抑制剂，但它们在临床试验中未能显示出有效性。现在，已经发现了两种具有不同功能的ACAT亚型ACAT 1和ACAT 2。因此，ACAT抑制剂对这两种亚型的选择性对于它们作为新型抗动脉粥样硬化剂的开发是重要的。选择性研究表明，真菌啶南平A（PPPA）是唯一的ACAT2特异性抑制剂。此外，PPPA在致动脉粥样硬化小鼠模型中被证明具有口服活性，表明其具有降低胆固醇和动脉粥样硬化保护活性。某些PPPA衍生物，半合成制备，具有更有效的和选择性的体外活性比PPPA对ACAT2。本文综述了ACAT 2特异性抑制剂的研究进展，并对ACAT 2特异性抑制剂的研究前景进行了展望。
Acyl-CoA:cholesterol acyltransferase (ACAT) is a promising therapeutic target for cardiovascular diseases. Although a number of synthetic ACAT inhibitors have been developed, they have failed to show efficacy in clinical trials. Now, the presence of two ACAT isoforms with distinct functions, ACAT1 and ACAT2, has been discovered. Thus, the selectivity of ACAT inhibitors toward the two isoforms is important for their development as novel anti-atherosclerotic agents. The selectivity study indicated that fungal pyripyropene A (PPPA) is only an ACAT2-specific inhibitor. Furthermore, PPPA proved orally active in atherogenic mouse models, indicating it possessed cholesterol-lowering and atheroprotective activities. Certain PPPA derivatives, semi-synthetically prepared, possessed more potent and selective in vitro activity than PPPA against ACAT2. This review covers these studies and describes the future prospects of ACAT2-specific inhibitors.
登录
查看更多内容
影响因子：
158.5
作者：
Cuchel, Marina;Bloedon, LeAnne T.;Rader, Daniel J.
通讯作者：
Rader, Daniel J.
DOI：
10.1016/s0021-9258(19)36846-2
发表时间：
1993-10
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
C. Chang;H. Huh;K. Cadigan;Ta-Yuan Chang
通讯作者：
C. Chang;H. Huh;K. Cadigan;Ta-Yuan Chang
影响因子：
24
作者：
Libby, P
通讯作者：
Libby, P
影响因子：
15.9
作者：
ISHIBASHI, S;BROWN, MS;HERZ, J
通讯作者：
HERZ, J
影响因子：
15.9
作者：
Accad, M;Smith, SJ;Farese, RV
通讯作者：
Farese, RV