Novel Bone Marrow Sparing Anticancer Salicyclic Amide Derivatives With In Vivo Activity Against Myeloma

Using a novel algorithm to screen small molecules for activity against multiple myeloma (MM) in the context of liver, kidney-like clearance, and both myeloma supporting as well as hematopoietic bone marrow, we identified three normal bone marrow sparing antimyeloma compounds from a 30,355 library of chemically diverse small molecules. CCF1172 was one of them. It had uniform activity against seven genetically heterogeneous MM cell lines, and demonstrated in vivo activity in a mouse model of myeloma. Medicinal chemistry modifications are currently underway and we anticipate these will lead to an optimized analog for use in myeloma and possibly other cancers. Activity has been demonstrated against seven genetically heterogeneous multiple myeloma cell lines and in a mouse model of myeloma. Jason Ospina ospinaj2@ccf.org 216-445-2330

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