Wu Donglin, Ding Zihui, Lu Tao, Chen Yadong, Zhang Feng, Lu Shuai
School of Science, China Pharmaceutical University, Nanjing 211198, China.
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Drug Discov Today. 2024 May;29(5):103975. doi: 10.1016/j.drudis.2024.103975. Epub 2024 Apr 4.
Discoidin domain receptor (DDR)-1 has a crucial role in regulating vital processes, including cell differentiation, proliferation, adhesion, migration, invasion, and matrix remodeling. Overexpression or activation of DDR1 in various pathological scenarios makes it a potential therapeutic target for the treatment of cancer, fibrosis, atherosclerosis, and neuropsychiatric, psychiatric, and neurodegenerative disorders. In this review, we summarize current therapeutic approaches targeting DDR1 from a medicinal chemistry perspective. Furthermore, we analyze factors other than issues of low selectivity and risk of resistance, contributing to the infrequent success of DDR1 inhibitors. The complex interplay between DDR1 and the extracellular matrix (ECM) necessitates additional validation, given that DDR1 might exhibit complex and synergistic interactions with other signaling molecules during ECM regulation. The mechanisms involved in DDR1 regulation in cancer and inflammation-related diseases also remain unknown.
盘状结构域受体（DDR）-1在调节包括细胞分化、增殖、黏附、迁移、侵袭和基质重塑等重要过程中发挥着关键作用。在各种病理情况下，DDR1的过表达或激活使其成为治疗癌症、纤维化、动脉粥样硬化以及神经精神、精神和神经退行性疾病的潜在治疗靶点。在本综述中，我们从药物化学角度总结了目前针对DDR1的治疗方法。此外，我们分析了除低选择性和耐药风险问题之外，导致DDR1抑制剂成功率不高的其他因素。鉴于DDR1在细胞外基质（ECM）调节过程中可能与其他信号分子表现出复杂的协同相互作用，DDR1与ECM之间复杂的相互作用需要进一步验证。DDR1在癌症和炎症相关疾病中的调节机制也尚不清楚。
