DDR1激酶是一个能够被胶原基质特异性的活化的受体络氨酸激酶，它在多种癌症中显示出了表达和功能异常。一些初步的生化基础研究表明它可能与癌症细胞的形态，增殖，生长，粘连以及转移有关，但相关的具体生理和病理研究目前还处于起步阶段。而缺乏高活性高选择性的DDR1激酶抑制剂是目前阻碍进一步深入研究其机理的主要因素。由于type II（二型）激酶抑制剂相对于type I激酶抑制剂在提高选择性方面有诸多优势，我们基于前期在type II激酶抑制剂方面的一些工作基础，拟利用片段组合的方法，采用计算机辅助设计和虚拟筛选与试验检测相结合的手段，开发新型的靶向于DDR1 激酶的type II激酶抑制剂，以验证DDR1作为新的抗癌症药物靶点的有效性。

The discoidin domain receptors (DDRs) kinases are a novel class of receptor tyrosine kinases that are activated by several collagens and known to be key regulators of cellular morphogenesis, differentiation, proliferation and adhesion/migration. Recent studies have shown altered expression of DDR1 in human tumors, including lung, esophageal, breast, ovary, and pediatric brain cancers, suggesting a definite role of DDR1 in tumor progression. The mechanism of how this receptor may contribute to oncogenesis is still unclear. However, given its important role in transmitting signals from the extracellular matrix (ECM), it is possible that it may act as a critical regulator of cell proliferation, adhesion, migration, and subsequent tumor metastasis. As yet, there is relatively little information concerning DDR1 downstream signaling pathways and functions. It has been well accepted that type II kinase inhibitors bear higher potential to exhibit better selectivity over type I kinase inhibitors. Based on the preliminary result in our lab for developing type II kinase inhibitors, we propose to use fragment hybrid approach to develop new and selective type II DDR1 kinase inhibitors to determine the pharmacological consequences of acute inhibition of DDR1 kinase activity in cancer background.