Preclinical Development
Several preclinical efficacy and safety studies have been conducted with SLx-2119.
Efficacy
SLx-2119 has been identified as a potent, highly selective
inhibitor of ROCK2 in vitro, The compound
inhibits stress fiber formation, cellular
migration, and endothelial cell tube
formation in vitro, and inhibits
angiogenesis in Matrigel® plug assays in
vivo, establishing its activity as a
ROCK2 inhibitor in cells and in vivo.
In preclinical studies, SLx-2119 has demonstrated efficacy in
fibrotic, liver steatosis and oncology models.
In the UUO model, treatment with SLx-2119 resulted in a
marked decrease in macrophage infiltration,
fibronectin and TNFa
expression.
In an ApoE atherosclerotic model, 10 weeks of
daily oral dosing with SLx-2119 produced more
than a 50% reduction in atherosclerotic plaque
in comparison to untreated animals.
In mouse xenograft models (HT-1080, Panc-1, and
MDA-MB-231 cancer cell lines), SLx-2119 has
demonstrated excellent
in vivo
cytostatic activity both as a single agent
and when combined with clinically approved agents
doxorubicin, gemcitabine and taxol.
Safety
No significant toxicity has been observed at doses up to ten times the efficacious dose of SLx-2119.
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