发现大环组蛋白去乙酰化酶 1、2 和 3 选择性抑制剂，用于 HIV 潜伏再激活。
Discovery of macrocyclic HDACs 1, 2, and 3 selective inhibitors for HIV latency reactivation.
机构信息
Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA.
Merck & Co., Inc., 770 Sumneytown Pike, West Point, PA 19486, USA.
出版信息
Bioorg Med Chem Lett. 2021 Sep 1;47:128168. doi: 10.1016/j.bmcl.2021.128168. Epub 2021 Jun 4.
A series of unique macrocyclic HDACs 1, 2, and 3 selective inhibitors were identified with good enzymatic activity and high selectivity over HDACs 6 and 8. These macrocyclic HDAC inhibitors used an ethyl ketone as the zinc-binding group. Compounds 25 and 26 stood out as leads due to their low double-digit nM ECs in the 2C4 cell-based HIV latency reactivation assay. The PK profiles of these macrocyclic HDAC inhibitors still needed improvement.
一系列独特的大环组蛋白去乙酰化酶 1、2 和 3 选择性抑制剂被鉴定出来，具有良好的酶活性和对组蛋白去乙酰化酶 6 和 8 的高选择性。这些大环组蛋白去乙酰化酶抑制剂使用乙基酮作为锌结合基团。化合物 25 和 26 因其在基于 2C4 细胞的 HIV 潜伏再激活测定中的低双位数 nMECs 而脱颖而出。这些大环组蛋白去乙酰化酶抑制剂的 PK 特征仍需要改进。
Zotero 插件