E-Selectin-CXCR4 Antagonist

GlycoMimetics has designed and synthesized a family of compounds that target both E-Selectin and CXCR4. CXCR4 has been successfully targeted by the approved drug plerixaflor, which is marketed by Sanofi as Mozobil. The drug has been approved for use to improve stem cell mobilization for transplant and is in clinical trials for use in combination with chemotherapy in hematological malignancies (types of cancer that affect blood, bone marrow, and lymph nodes). Thus, targeting CXCR4 has demonstrated clinical benefit in certain settings. Also, data presented at the December 2011 American Society of Hematology (ASH) meeting has shown in a model of acute myeloid leukemia (AML) that compounds from this compound family, combined with chemotherapy, enhanced clearance of blast cells from the bone marrow, compared to chemotherapy alone. We are exploring use of compounds in this family in preclinical models of a variety of cancers, particularly those prone to metastasis to the bone.

Combining E-Selectin and CXCR4 targeting in a single molecule may provide next-generation opportunities following on the success of Mozobil and other potential drugs in this class, particularly for treatment of certain blood cancers and cancers involving metastasis to bone.