Feng Rentian, Lentzsch Suzanne
Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15232, USA.
Drug News Perspect. 2007 Sep;20(7):431-5. doi: 10.1358/dnp.2007.20.7.1149631.
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.
多发性骨髓瘤（MM）是一种血液系统恶性肿瘤，其特征为浆细胞增殖失调以及破骨细胞活性增加，进而导致骨质破坏和溶骨性病变。因此，针对骨髓瘤细胞和破骨细胞功能的新型治疗方式可能会显著改善MM患者的预后。作为环氧化酶（COX）抑制剂依托度酸的R-对映体，SDX-101已显示出良好的抗骨髓瘤作用。最近，依托度酸的另一种结构类似物SDX-308在肿瘤细胞系上表现出体外细胞毒性活性，并在小鼠体内显示出抗肿瘤功效。SDX-308具有高抗骨髓瘤活性，并且在与其他药物联合治疗慢性淋巴细胞白血病（CLL）时表现出协同作用。此外，SDX-308抑制破骨细胞（OCL）形成，从而完全消除骨吸收。因此，SDX-308可能是治疗破骨细胞活性增加的疾病（如多发性骨髓瘤和转移性癌中的溶骨性病变以及骨质疏松症）的一种有吸引力的药物。在本综述中，我们讨论了SDX-308作为治疗MM和破骨细胞活性增加的疾病的一种新的治疗候选药物。
