Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
Chin J Nat Med. 2013 Sep;11(5):506-13. doi: 10.1016/S1875-5364(13)60092-8.
Protein tyrosine kinases (PTKs) are attractive targets in searching for therapeutic agents against many diseases. In this study, a series of dehydroabietylamine derivatives were first determined to show PTK inhibitory activity using a high-throughput screening (HTS) method based on homogeneous time-resolved fluorescence (HTRF) technology. The structure-activity relationships of the dehydroabietylamine derivatives were established, and it was found that the compounds with a nitrogen-containing side chain had better inhibitory activity. Further studies showed that the compounds substituted with halogen in the phenyl ring resulted in higher inhibitory activity on the epidermal growth factor receptor (EGFR), and can be a guide to modify the structure of dehydroabietylamine derivatives. Dehydroabietylamine derivatives might be a new class of multi-targeted and effective PTK inhibitors with structure modifications.
蛋白酪氨酸激酶（PTKs）是寻找治疗多种疾病的治疗药物的有吸引力的靶点。在这项研究中，首次使用基于均相时间分辨荧光（HTRF）技术的高通量筛选（HTS）方法确定了一系列去氢枞胺衍生物具有 PTK 抑制活性。建立了去氢枞胺衍生物的构效关系，发现具有含氮侧链的化合物具有更好的抑制活性。进一步的研究表明，苯环上带有卤素取代基的化合物对表皮生长因子受体（EGFR）具有更高的抑制活性，可以作为修饰去氢枞胺衍生物结构的指导。去氢枞胺衍生物可能是一类新型的多靶点、有效的具有结构修饰的 PTK 抑制剂。
