Kamakura Research Laboratories, Chugai Pharmaceutical Co. Ltd., Kamakura, Kanagawa, Japan.
Bioorg Med Chem Lett. 2011 Jun 15;21(12):3788-93. doi: 10.1016/j.bmcl.2011.04.020. Epub 2011 Apr 22.
Anaplastic lymphoma kinase (ALK) receptor tyrosine kinase is considered a promising therapeutic target for human cancers. We identified novel tetracyclic derivatives as potent ALK inhibitors. Among them, compound 27 showed strong cytotoxicity against KARPAS-299 with an IC(50) value of 21 nM and significant antitumor efficacy in ALK fusion-positive blood and solid cancer xenograft models in mice without body weight loss.
间变性淋巴瘤激酶 (ALK) 受体酪氨酸激酶被认为是人类癌症有前途的治疗靶点。我们鉴定了新型四环衍生物作为有效的 ALK 抑制剂。其中，化合物 27 对 KARPAS-299 具有很强的细胞毒性，IC50 值为 21 nM，并且在携带 ALK 融合基因的血液肿瘤和实体瘤异种移植模型中具有显著的抗肿瘤疗效，无体重减轻。
