Design of a Supersoft Topical JAK Inhibitor, Which Is Effective in Human Skin but Rapidly Deactivated in Blood
1. 系统已在2025-10-03 11:40:02对应助文件进行删除
2. 如有需要请重新发布求助信息
注: 所有应助的资源仅供学习交流使用, 不得违反相关法律法规
DOI:
文献链接:
其他信息:
G Thoma, O Decoret, E Vangrevelinghe…
Journal of medicinal …, 2023
ACS Publications
We describe the discovery and characterization of the supersoft topical JAK inhibitor 3 (R), which is potent in biochemical and cellular assays as well as in human skin models. In blood, the neutral ester 3 (R) is rapidly hydrolyzed (t 1/2∼ 6 min) to the corresponding charged carboxylic acid 4 exhibiting> 30-fold reduced permeability. Consequently, acid 4 does not reach the intracellular JAK kinases and is inactive in cellular assays and in blood. Thus, hydrolysis by blood esterases leads to the rapid deactivation of topically active ester 3 …
