AN OPEN-LABEL STUDY OF THE EFFICACY, SAFETY, AND TOLERABILITY OF ORAL SCIO-469

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。多发性骨髓瘤(MM)是一种无法治愈的恶性肿瘤，标准治疗的中位生存期约为三年。它占恶性血液肿瘤的10%，估计每年有10,800人死亡。这种疾病的高死亡率和发病率，加上最近对细胞因子在MM发病机制中作用的了解的增加，促使人们使用新的治疗方法进行研究，从而有可能改善患者的预后。SCiO-469是一种口服活性的新化学实体，它抑制P38A丝裂原活化蛋白激酶(MAPK)，具有抗炎和改善疾病的作用，目前处于类风湿关节炎的II期临床开发阶段，已显示出能够影响参与MM发病的细胞因子IL-6、血管内皮生长因子(VEGF)、肿瘤坏死因子(TNFa)和IL-1B。P38A MAPK介导促炎细胞因子和其他因子的产生，包括前列腺素(PGE)2受体核因子-kB连接激活剂(RANKL)和IL-11，影响MM的发病机制。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Multiple Myeloma (MM) is an incurable malignancy with a median survival of approximately three years with standard therapy. It accounts for 10% of malignant hematologic neoplasm with an estimated 10,800 deaths per year. The high mortality and morbidity of the disease, coupled with recent increased understanding of the role of cytokines in the pathogenesis of MM, have stimulated investigations using novel treatments that offer the potential to improve patient outcome. SCIO-469, an orally active new chemical entity that inhibits p38a mitogen-activated protein kinase (MAPK), with demonstrated anti-inflammatory and disease-modifying properties currently in Phase II clinical development for rheumatoid arthritis, has shown the ability to influence the cytokines, IL-6, vascular endothelial growth factory (VEGF), TNFa, and IL-1B involved in the pathogenesis of MM. P38a MAPK mediates the production of proinflammatory cytokines and other factors, including prostaglandin (PGE)2 receptor activator of nuclear factor-kB ligand (RANKL), and IL-11, that affect the pathogenesis of MM.