Selective oral ROCK2 inhibitor down-regulates IL-21 and IL-17 secretion in human T cells via STAT3-dependent mechanism.

@article{ZaninZhorov2014SelectiveOR,
  title={Selective oral ROCK2 inhibitor down-regulates IL-21 and IL-17 secretion in human T cells via STAT3-dependent mechanism.},
  author={Alexandra Zanin-Zhorov and Jonathan Matthew Weiss and Melanie S. Nyuydzefe and Wei Chen and Jose U Scher and Rigen Mo and David Depoil and Narsing A. Rao and Ben Liu and Jianlu Wei and Sarah Drews Lucas and Matthew Koslow and Mar{\'i}a Luz Roche and Olivier Schueller and Sara O. Weiss and Masha V. Poyurovsky and James R. Tonra and Keli L Hippen and Michael Loran Dustin and Bruce R Blazar and Chuan-Ju Liu and Samuel D. Waksal},
  journal={Proceedings of the National Academy of Sciences of the United States of America},
  year={2014},
  volume={111 47},
  pages={
          16814-9
        }
}
Rho-associated kinase 2 (ROCK2) regulates the secretion of proinflammatory cytokines and the development of autoimmunity in mice. Data from a phase 1 clinical trial demonstrate that oral administration of KD025, a selective ROCK2 inhibitor, to healthy human subjects down-regulates the ability of T cells to secrete IL-21 and IL-17 by 90% and 60%, respectively, but not IFN-γ in response to T-cell receptor stimulation in vitro. Pharmacological inhibition with KD025 or siRNA-mediated inhibition of… CONTINUE READING

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