Cancer and Infectious Disease Research Center, Division of Drug Discovery Research, Korea Research Institute of Chemical Technology, Daejeon, 305-600, Republic of Korea.
Arch Pharm Res. 2013 Sep;36(9):1051-4. doi: 10.1007/s12272-013-0157-8. Epub 2013 May 23.
The anaplastic lymphoma kinase (ALK) receptor tyrosine kinase represents a potential therapeutic target. Specially, a variety of alterations in the ALK gene including mutations, overexpression, amplification, translocations and structural rearrangements, are involved in human cancer tumorigenesis. The second-generation ALK inhibitor CH5424802 (development code: AF802; Chugai Pharmaceutical, a subsidiary of Roche) achieves tumor regression with excellent tolerance and shows promising efficacy in patients with ALK-positive non-small cell lung cancer. CH5424802 shows good kinase selectivity, has a promising pharmacokinetics profile, and has strong antiproliferative activity in several ALK-driven tumor models. CH5424802 has also shown anti-tumor activity in mouse xenograft studies. Here, we summarize recent advances and the evidence that CH5424802 acts as an ALK inhibitor. We also discuss its potential for further development as an anticancer drug in clinical trials.
间变性淋巴瘤激酶（ALK）受体酪氨酸激酶是一个潜在的治疗靶点。特别是，ALK 基因的各种改变，包括突变、过表达、扩增、易位和结构重排，都参与了人类癌症的肿瘤发生。第二代 ALK 抑制剂 CH5424802（开发代码：AF802；罗氏子公司中外制药）具有良好的耐受性，能实现肿瘤消退，并在 ALK 阳性非小细胞肺癌患者中显示出有前景的疗效。CH5424802 具有良好的激酶选择性，具有有前景的药代动力学特征，在几种 ALK 驱动的肿瘤模型中具有很强的抗增殖活性。CH5424802 在小鼠异种移植研究中也显示出抗肿瘤活性。在这里，我们总结了 CH5424802 作为 ALK 抑制剂的最新进展和证据。我们还讨论了它在临床试验中作为抗癌药物进一步开发的潜力。
