Treatment of multiple myeloma with SDX-308.
Multiple myeloma (MM) is a hematologic malignancy characterized by dysregulated proliferation of plasma cells and increased osteoclast activity that results in bone destruction and lytic lesions. Therefore, novel treatment modalities targeting both myeloma cell and osteoclast function may dramatically improve MM patient outcome. As an R-enantiomer of the cyclooxygenase (COX) inhibitor etodolac, SDX-101 has shown favorable antimyeloma effects. More recently, another structural analogue of etodolac, SDX-308, has displayed in vitro cytotoxic activity on tumor lines and in vivo antitumor efficacy in mice. SDX-308 has high antimyeloma activity and shows synergism in combination with other drugs for the treatment of chronic lymphocytic leukemia (CLL). In addition SDX-308 inhibits osteoclast (OCL) formation resulting in complete abrogation of bone resorption. Therefore, SDX-308 might be an attractive drug for the treatment of diseases with increased OCL activity, such as osteolytic lesions in multiple myeloma and metastatic carcinomas as well as osteoporosis. In the present review, we discuss SDX-308 as a new therapeutic candidate for the treatment of MM and diseases with increased osteoclast activity.
Feng
Rentian
R
Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15232, USA.
Lentzsch
Suzanne
S
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001847:Bone Diseases / Q000188:drug therapy*; D004358:Drug Therapy / Q000639:trends; D017308:Etodolac / Q000627:therapeutic use*; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000503:physiopathology; D010010:Osteoclasts / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D006575:Heterocyclic Compounds, 3-Ring; C518129:SDX 308; D014409:Tumor Necrosis Factor-alpha; D017308:Etodolac