Nat Rev Drug Discov. 2012 Jun 1;11(6):437-8. doi: 10.1038/nrd3753.
Vismodegib (GDC-0449), an orally bioavailable small molecule inhibitor of Hedgehog signaling, was recently approved by the U.S. Food and Drug Administration for the treatment of basal cell carcinoma that is either metastatic or locally advanced in patients who are not candidates for surgical resection or radiation. Given the absence of previously defined effective drug therapy for this disease, approval was granted based primarily on outcome of a non-randomized parallel cohort phase II study of 99 patients with advanced basal cell carcinoma, with a primary endpoint of objective response rate. Response rates of 30.3 and 42.9 percent were observed in metastatic and locally advanced cohorts in this study, respectively, associated with median progression-free survival in both cohorts of 9.5 months. Ongoing clinical investigations include evaluation of the potential efficacy of vismodegib in a variety of disease contexts, and in combination with other agents. The mechanism of action, preclinical and clinical data, and potential utility in other disease contexts are reviewed.
维莫德吉（GDC-0449）是一种口服生物可利用的 Hedgehog 信号小分子抑制剂，最近被美国食品和药物管理局批准用于治疗不适合手术切除或放疗的转移性或局部晚期基底细胞癌患者。鉴于这种疾病以前没有明确的有效药物治疗方法，批准主要基于对 99 名晚期基底细胞癌患者的非随机平行队列二期研究的结果，主要终点是客观缓解率。在这项研究中，转移性和局部晚期队列的反应率分别为 30.3%和 42.9%，与两个队列的中位无进展生存期均为 9.5 个月相关。正在进行的临床研究包括评估维莫德吉在各种疾病情况下的潜在疗效，以及与其他药物联合使用的情况。本文综述了其作用机制、临床前和临床数据，以及在其他疾病情况下的潜在应用。
