Al-Obeidi F A, Lam K S
Selectide Corporation, A Subsidiary of Avantis., 1580 E. Hanely Blvd., Tucson, Arizona, AZ 85737, USA.
Oncogene. 2000 Nov 20;19(49):5690-701. doi: 10.1038/sj.onc.1203926.
In the last 5 years, through combinatorial chemistry, high-throughput screening, computational chemistry, and traditional medicinal chemistry, numerous inhibitors for various protein tyrosine kinases (PTKs) have been developed. The majority of these compounds are small molecules that compete at the ATP binding site of the catalytic domain of the enzymes. Some compounds such as pseudosubstrate-based peptide inhibitor binds to the peptide/protein substrate site of the catalytic domain. Some inhibitors, primarily monoclonal antibodies, bind to the extracellular domain of receptor tyrosine kinases. Some of these inhibitors are highly potent and selective. Several are currently undergoing clinical trials for a number of diseases such as cancer.
在过去5年中，通过组合化学、高通量筛选、计算化学和传统药物化学，已开发出多种针对各种蛋白酪氨酸激酶（PTK）的抑制剂。这些化合物大多是小分子，它们在酶催化结构域的ATP结合位点进行竞争。一些化合物，如基于假底物的肽抑制剂，与催化结构域的肽/蛋白质底物位点结合。一些抑制剂，主要是单克隆抗体，与受体酪氨酸激酶的细胞外结构域结合。其中一些抑制剂具有高效性和选择性。目前有几种正在针对多种疾病（如癌症）进行临床试验。
