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Related Experiment Video

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Targeting ROCK2 for Atopic Dermatitis Relief.

Weilong Liu1,2, Jianhua Ju3

  • 1State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Key Laboratory of Chemical Biology (Ministry of Education), Shandong Key Laboratory of Druggability Optimization and Evaluation for Lead Compounds, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, People's Republic of China.

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|February 27, 2026
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Summary

Researchers discovered compound 10d, a selective ROCK2 inhibitor inspired by natural products. This compound shows promise for treating atopic dermatitis (AD) by targeting ROCK2 effectively in preclinical models.

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Area of Science:

  • Biochemistry
  • Pharmacology
  • Immunology

Background:

  • Atopic dermatitis (AD) presents significant unmet therapeutic needs.
  • Current treatments for AD have limitations, necessitating novel strategies.
  • Rho-associated coiled-coil containing protein kinase 2 (ROCK2) is implicated in AD pathogenesis.

Purpose of the Study:

  • To report the discovery and preclinical evaluation of compound 10d, a selective ROCK2 inhibitor.
  • To investigate the therapeutic potential of targeting ROCK2 for atopic dermatitis.
  • To validate a novel hydrophobic surface on ROCK2 as a basis for inhibitor design.

Main Methods:

  • Structure-based drug design utilizing a novel hydrophobic surface unique to ROCK2.
  • Synthesis and characterization of compound 10d, a natural product-inspired ROCK2 inhibitor.
  • Evaluation of compound 10d efficacy in a MC903-induced mouse model of atopic dermatitis.

Main Results:

  • Compound 10d was identified as a potent and selective ROCK2 inhibitor.
  • The compound demonstrated significant efficacy in ameliorating AD-like skin inflammation in a mouse model.
  • ROCK2 inhibition proved effective in reducing key inflammatory markers associated with atopic dermatitis.

Conclusions:

  • Selective ROCK2 inhibition represents a promising therapeutic strategy for atopic dermatitis.
  • Compound 10d serves as a lead compound for further development in AD treatment.
  • Targeting the identified hydrophobic surface on ROCK2 offers a viable approach for drug discovery.