Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Artículo científico |
| Language: | en |
| Published: |
Journal of medicinal chemistry
2026
|
| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/41574563/ |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Table of Contents:
- Design, Synthesis, and Evaluation of a Potent and Selective ROCK2 Inhibitor for Atopic Dermatitis Treatment. Mao, Churu Zhan, Shuai Fang, Zhangyun Fang, Jiebin Huang, Yun Ding, Wanjing Ma, Zhongjun rho-Associated Kinases Animals Dermatitis, Atopic Drug Design Mice Protein Kinase Inhibitors Humans Structure-Activity Relationship Atopic dermatitis (AD) remains a significant clinical challenge due to the limited efficacy and safety concerns associated with current therapies. To address this unmet need, we utilized structure-guided analysis and identified a previously unrecognized hydrophobic surface () unique to ROCK2. Exploiting this structural feature through virtual screening led to the discovery of compound , a potent ROCK2 inhibitor with markedly improved selectivity compared to the reference compound . In a mouse model of MC903-induced AD, effectively suppressed inflammation and achieved therapeutic efficacy superior to the model group, while maintaining a favorable safety profile. Mechanistically, we demonstrated that attenuates AD pathology by downregulating , highlighting the ROCK2-S100A9 axis as a novel pathway in AD pathogenesis. Collectively, these findings establish as a highly active and selective inhibitor, marking the first exploration of ROCK2-targeted therapy for AD treatment.