Multiple myeloma is a neoplastic plasma-cell disorder and it remains uniformly fatal because of intrinsic or acquired drug resistance. Accordingly, the median survival time for multiple myeloma patients is merely 3 to 5 years despite the development of new drugs, and there is an urgent need for combating this deadly disease with novel therapeutic strategies. The progression and survival of multiple myeloma is dependent on its interaction with bone marrow microenvironment. CXCR4 receptor and its ligand SDF-1 are involved in the movement of cells and high levels of SDF-1 are found in the bone marrow. Myeloid cell leukemia 1 (MCL-1) is an important signaling protein that regulates intrinsic apoptosis and defective apoptotic signaling is a hallmark of many cancers. Accordingly, we hypothesize the design of a new drug, which inhibits the migration of myeloma cells to bone marrow and suppresses the expression of survival protein Mcl-1 would be a better option for the treatment of multiple myeloma with two mechanisms of action (namely dual inhibition of CXCR4 as well as Mcl-1). In this regard, we recently took up a project on the synthesis of novel drug candidates based on the natural product Gambogic acid. Our initial data suggests that this conjugate inhibits the cell proliferation, expression of CXCR4, Mcl-1, and other downstream targets of CXCR4 in multiple myeloma cells. Our synthetic and biological evaluation data will be presented.

Preparation and biological activity of CXC chemokine receptor 4 (CXCR4) and myeloid cell leukemia 1 (MCL-1) dual inhibitors

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.