Li Yupeng, Lu Xiaoyun, Ren Xiaomei, Ding Ke
†State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, No. 190 Kaiyuan Avenue, Guangzhou 510530, China.
‡University of Chinese Academy of Sciences, No. 19 Yuquan Road, Beijing 100049, China.
J Med Chem. 2015 Apr 23;58(8):3287-301. doi: 10.1021/jm5012319. Epub 2015 Jan 21.
Discoidin domain receptors (DDRs) are members of the transmembrane receptor tyrosine kinase (RTK) superfamily which are distinguished from others by the presence of a discoidin motif in the extracellular domain and their utilization of collagens as internal ligands. Two types of DDRs, DDR1 and DDR2, have been identified with distinct expression profiles and ligand specificities. These DDRs play important roles in the regulation of fundamental cellular process, such as proliferation, survival, differentiation, adhesion, and matrix remodeling. They have also been closely linked to a number of human diseases, including various fibrotic disorders, atherosclerosis, and cancer. As a consequence, DDRs have been considered as novel potential molecular targets for drug discovery and increasing efforts are being devoted to the identification of new small molecule inhibitors targeting the receptors. In this review, we offer a contemporary overview on the discovery of DDRs inhibitors and their potential medical application for the treatment of cancer and inflammation related disorders.
盘状结构域受体（DDRs）是跨膜受体酪氨酸激酶（RTK）超家族的成员，其在细胞外结构域中存在盘状结构域基序以及利用胶原蛋白作为内在配体，这使其有别于其他成员。已鉴定出两种类型的DDRs，即DDR1和DDR2，它们具有不同的表达谱和配体特异性。这些DDRs在调节诸如增殖、存活、分化、黏附及基质重塑等基本细胞过程中发挥重要作用。它们还与多种人类疾病密切相关，包括各种纤维化疾病、动脉粥样硬化和癌症。因此，DDRs被认为是药物研发的新型潜在分子靶点，并且人们正加大努力致力于鉴定靶向这些受体的新型小分子抑制剂。在本综述中，我们对DDRs抑制剂的发现及其在治疗癌症和炎症相关疾病方面的潜在医学应用进行了当代概述。
