TMPRSS6 inhibitor Cpd-B (TMPRSS6-IN-Cpd-B) is a highly potent (IC50=7.6 nM), specific small molecule inhibitor of TMPRSS6 (matriptase-2).
TMPRSS6 inhibitor Cpd-B shows no activity toward furin, wekaly inhibits other TTSP family members matriptase and hepsin, as well as factor Xa and thrombin.
TMPRSS6 inhibitor Cpd-B demonstrates cellualr IC50 (144 nM) in cell media of TMPRSS6-transfected HEK293 cells with no cytotoxicity, and no negatively affect TMPRSS6 plasma membrane localization.
Inhibiting TMPRSS6 proteolytic activity prevents cleavage of hemojuvelin (HJV) in HeLa cells (IC50=267 nM).
TMPRSS6 inhibition increases hepcidin encoding gene (HAMP) expression in HepG2 cells and human primary hepatocytes.
TMPRSS6, also known as matriptase-2, is a TTSP almost exclusively expressed at the surface of hepatocytes in the liver, and plays a key role in iron homeostasis via modulation of hepcidin expression.