School of Pharmacy and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, China.
School of Pharmacy, Zunyi Medical University, Zunyi, 563006, China.
Eur J Med Chem. 2022 Apr 5;233:114232. doi: 10.1016/j.ejmech.2022.114232. Epub 2022 Feb 25.
Bruton's tyrosine kinase (BTK) is a promising target in the treatment of various cancers. Despite the early success of BTK inhibitors in the clinic, these single-target drug therapies have limitations in their clinical applications, such as drug resistance. Several alternative strategies have been developed, including the use of dual inhibitors, to maximize the therapeutic potential of anticancer drugs. In this review, we highlight the scientific background and theoretical basis for developing BTK-based dual inhibitors, as well as the status of these agents in preclinical and clinical studies, and discuss further options in this field. We posit that these advances in BTK-based dual inhibitors confirm their feasibility for the treatment of refractory tumors, including those with drug resistance, and provide a framework for future drug design in this field. Accordingly, we anticipate increasingly rapid progress in the development of novel potent dual inhibitors and advanced clinical research on BTK-based dual inhibitors.
布鲁顿酪氨酸激酶（BTK）是治疗各种癌症的有前途的靶点。尽管 BTK 抑制剂在临床上早期取得了成功，但这些单靶标药物疗法在临床应用中存在局限性，例如耐药性。已经开发了几种替代策略，包括使用双重抑制剂，以最大限度地发挥抗癌药物的治疗潜力。在这篇综述中，我们强调了开发基于 BTK 的双重抑制剂的科学背景和理论基础，以及这些药物在临床前和临床研究中的地位，并讨论了该领域的进一步选择。我们认为，这些基于 BTK 的双重抑制剂的进展证实了它们在治疗难治性肿瘤方面的可行性，包括耐药性肿瘤，并为该领域的未来药物设计提供了框架。因此，我们预计新型强效双重抑制剂的开发和基于 BTK 的双重抑制剂的临床研究将取得越来越快的进展。
