GlycoMimetics has developed families of antagonists that bind to E-, P- and/or L-selectin.  Some of these compounds, such as our lead candidate GMI-1070, are pan-selectin antagonists, binding to all three of the selectins.  We have also developed a family of potent, small molecule E-selectin specific antagonists.

Elevated levels of E-selectin have been shown to correlate with increased risk of complications related to poor microvascular blood flow, such as diabetic retinopathy and nephropathy.  GlycoMimetics has discovered a potent E-selectin inhibitor, which in vitro, inhibits leukocyte rolling and adhesion increased by human serum proteins from diabetic patients. We believe that E-selectin antagonists could also be useful in treating certain inflammatory skin conditions where E-selectin plays an important role.

We have also identified additional potential infective disease targets, including and DC-SIGN. Successful strategies for infection among a wide range of pathogens have evolved and converged on DC-SIGN as an initial portal of infection.  This suggests that intervention at this molecular target may hold the promise for a new class of entry inhibitors to treat infectious disease. GlycoMimetics, Inc. is uniquely positioned to generate small molecule antagonists of DC-SIGN, since such antagonists would ideally mimic the carbohydrate structures that are the native ligands.  In initial in vitro studies, one of GlycoMimetics’ compounds has been shown to inhibit HIV binding to DC-SIGN-expressing cells.  Additional in vitro studies show that the compound inhibits infection by Dengue virus of DC-SIGN expressing cells.  Further work is on-going to generate more potent compounds and to evaluate other effects.