Rho-associated coiled-coil-containing
kinases (ROCKs),
serine/threonine
protein kinases, were initially identified as downstream targets of
the small GTP-binding protein Rho. Pulmonary fibrosis (PF) is a lethal
disease with limited therapeutic options and a particularly poor prognosis.
Interestingly, ROCK activation has been demonstrated in PF patients
and in animal PF models, making it a promising target for PF treatment.
Many ROCK inhibitors have been discovered, and four of these have
been approved for clinical use; however, no ROCK inhibitors are approved
for the treatment of PF patients. In this article, we describe ROCK
signaling pathways and the structure–activity relationship,
potency, selectivity, binding modes, pharmacokinetics (PKs), biological
functions, and recently reported inhibitors of ROCKs in the context
of PF. We will also focus our attention on the challenges to be addressed
when targeting ROCKs and discuss the strategy of ROCK inhibitor use
in the treatment of PF.
In Figure 3d, the x-axis '1-8 days of treatment' was incorrectly given as '0-7 days of treatment' . The correct Figure 3d appears below as Fig. 1. Figure 1.
OPEN
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