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MDPK67b is a recombinant protease inhibitor which targets human kallikrein 2 (hK2) for the treatment of prostate cancer. MDPK67b was developed at Med Discovery using our expertise in kallikreins and protease inhibitors. Based on the natural serine protease inhibitor ACT (alpha1-antichymotrypsin) with only four amino-acid changes, we have developed a highly active and selective inhibitor for hK2. The compound has completed first in man trials in healthy volunteers in 2017.
(hK2) protein is a prostate-specific serine protease. This protease is involved in prostate cancer development where its activity correlates with prostate cancer aggressiveness, unlike PSA. Its expression increases incrementally from benign epithelium to prostatic epithelial neoplasia to prostate cancer.
The effect of hK2 expression in prostate cancer was evaluated in a mouse model. Wild type human prostate cancer DU-145 cells, which do not express hK2 or DU145-hK2 cells, expressing enzymatically active hK2 at levels detected in patients with prostate cancer, were grafted into nude mice. Analysis of the tumor growth in the two models clearly demonstrated that hK2 secretion in DU145-hK2 cells increased the tumor implantation rate and stimulated growth of human prostate cancer tumors in the mice.
Its numerous proteolytic activities suggest that hK2 contributes to cancer progression and development: