SDX-308 and SDX-101, non-steroidal anti-inflammatory drugs, as therapeutic candidates for treating hematologic malignancies including myeloma.
Non-steroidal anti-inflammatory drugs have been shown to inhibit carcinogenesis in colon cancer, and to induce apoptosis in a variety of tumor cell lines. Some anti-tumor effects are thought to be related to their cyclooxygenase-2-inhibitory activity, but recent studies have shown that non-steroidal anti-inflammatory drugs exert their anti-tumor effect via cyclooxygenase-2-independent mechanism. SDX-308 (CEP-18082) is a non-cyclooxygenase-2-inhibiting indole-pyran analog and is structurally related to SDX-101, an R-enantiomer of etodolac. SDX-308 has a potent anti-myeloma effect and shows synergism in combination with other drugs for the treatment of chronic lymphocytic leukemia. In addition SDX-308 inhibits osteoclast formation and activity and thereby might be an attractive drug for the treatment of diseases with increased osteoclast activity such as osteolytic lesions in multiple myeloma and metastatic carcinomas, as well as osteoporosis. This review covers future application of SDX-308 as an anti-myeloma drug regulating increased osteoclast activity.
Lentzsch
Suzanne
S
University of Pittsburgh Cancer Institute, Division of Hematology/Oncology, Pittsburgh, PA 15232, USA. lentzschs@upmc.edu
Elliott
Gary
G
Roodman
G David
GD
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017308:Etodolac / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D019337:Hematologic Neoplasms / Q000188:drug therapy*; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects / Q000502:physiology; D013237:Stereoisomerism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D006575:Heterocyclic Compounds, 3-Ring; D016328:NF-kappa B; C518129:SDX 308; D017308:Etodolac