cts-1027

Description: CTS-1027 is a novel, potent small molecule inhibitor of MMPs (matrix metalloproteinase) with IC50s of 0.3 nM, 0.5 nM for MMP2, MMP13, respectively, and has > 1, 000 fold selectivity over MMP1. Excessive matrix metalloproteinase (MMP) activity has been implicated in the pathogenesis of acute and chronic liver injury. CTS-1027 is an MMP inhibitor, which has previously been studied in humans as an anti-arthritic agent. BDL mice treated with CTS-1027 demonstrated a threefold reduction in hepatocyte apoptosis as assessed by the TUNEL assay or immunohistochemistry for caspase 3/7-positive cells as compared to vehicle-treated BDL animals (P < 0.01). A 70% reduction in bile infarcts, a histological indicator of liver injury, was also observed in CTS-1027-treated BDL animals. These differences could not be ascribed to differences in cholestasis as serum total bilirubin concentrations were nearly identical in the BDL groups of animals. Markers for stellate cell activation (alpha-smooth muscle actin) and hepatic fibrogenesis (collagen 1) were reduced in CTS-1027 versus vehicle-treated BDL animals (P < 0.05). Overall animal survival following 14 days of BDL was also improved in the group receiving the active drug (P < 0.05).

References: Hepatol Res. 2009 Aug; 39(8):805-813.; Cardiovasc Res. 2006 Aug 1; 71(3):586-595.