Boronic acids have been widely used in medicinal chemistry, notably as warheads of reversible covalent inhibitors of proteases, including two approved drugs (Bortezomib and Ixazomib for the treatment of relapsed multiple myeloma and mantle cell lymphoma). In addition, boronic acids are remarkably stable despite their high reactivity and consistently display very low toxicology profiles. Consequently, we designed our bicyclic boropeptides to be structurally close to Talabostat (Figure ), a multi-target inhibitor, which entered Phase III clinical trials for the treatment of advanced non-small cell lung cancer. However, Talabostat displayed a loss in efficacy in vivo believed to be a result of a reversible intramolecular cyclization into an inactive cyclic adduct. The constrained scaffold of our designed boronic acids 10f, 11b, 12c, and 13b