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| Natura: | Artículo científico |
| Lingua: | en |
| Pubblicazione: |
Journal of medicinal chemistry
2026
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| Soggetti: | |
| Accesso online: | https://pubmed.ncbi.nlm.nih.gov/41574563/ |
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| _version_ | 1868266095185494018 |
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| author | Mao, Churu Zhan, Shuai Fang, Zhangyun Fang, Jiebin Huang, Yun Ding, Wanjing Ma, Zhongjun |
| author_facet | Mao, Churu Zhan, Shuai Fang, Zhangyun Fang, Jiebin Huang, Yun Ding, Wanjing Ma, Zhongjun Mao, Churu Zhan, Shuai Fang, Zhangyun Fang, Jiebin Huang, Yun Ding, Wanjing Ma, Zhongjun |
| collection | PubMed - marine biology |
| 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. |
| format | Artículo científico |
| id | pubmed_41574563 |
| institution | PubMed |
| language | en |
| publishDate | 2026 |
| publisher | Journal of medicinal chemistry |
| record_format | pubmed |
| spellingShingle | 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 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. |
| title | Design, Synthesis, and Evaluation of a Potent and Selective ROCK2 Inhibitor for Atopic Dermatitis Treatment. |
| topic | rho-Associated Kinases Animals Dermatitis, Atopic Drug Design Mice Protein Kinase Inhibitors Humans Structure-Activity Relationship |
| url | https://pubmed.ncbi.nlm.nih.gov/41574563/ |