The heparan sulfate degrading enzyme, heparanase, promotes myeloma growth and metastasis. Heparanase expression correlates with myeloma tumor vascularity and bone metastasis, indicating that the enzyme is an important target for drug development. Our previously developed heparanase inhibitor successfully inhibits myeloma tumor growth and metastasis in preclinical models.
Based upon our newly resolved heparanase crystal structure we now propose to: i) ameliorate the existing heparin-mimicking heparanase inhibitor, and ii) rationally design small molecules and antibodies directed against heparanase. We hope that this project will have straightforward application in the treatment of multiple myeloma.