Publications by authors named "Michael Maddalena"
A focused drug repurposing approach is described where an FDA-approved drug is rationally selected for biological testing based on structural similarities to a fragment compound found to bind a target protein by an NMR screen. The approach is demonstrated by first screening a curated fragment library using F NMR to discover a quality binder to ACE2, the human receptor required for entry and infection by the SARS-CoV-2 virus. Based on this binder, a highly related scaffold was derived and used as a "smart scaffold" or template in a computer-aided finger-print search of a library of FDA-approved or marketed drugs.
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- The IRIS study investigated the safety and effectiveness of low molecular weight heparin (LMWH) compared to unfractionated heparin (UFH) in elderly patients (≥70 years) with impaired renal function and deep vein thrombosis (DVT).
- The trial included 539 patients, who were randomized to receive either tinzaparin or UFH, but was halted early due to a higher mortality rate in the tinzaparin group (11.5% vs. 6.3%).
- Results showed similar rates of bleeding and recurrent venous thromboembolism between both groups, suggesting the mortality difference might be linked to pre-existing risk factors, emphasizing the challenges in studying frail elderly populations.