The TAM (Axl, Mer, and Tyro3) family is implicated in the survival and chemoresistance of tumours and has emerged as a potential therapeutic target. A novel series of 7-aryl-2-anilino-pyrrolopyrimidines were identified as potent Axl/Mer tyrosine kinase inhibitors without significant inhibition of Tyro3. A representative compound 27 exhibited IC₅₀ values of 2 nM and 16 nM for Mer and Axl, respectively, and considerable inhibition for Mer phosphorylation in cells. Docking studies suggested that the formation of a salt bridge between the nitrogen of the aniline moiety with ASP678 of the Mer kinase domain as well as an interaction with the hinge region that most kinase inhibitors have in common would be essential to retain activity. These results could provide useful information for finding promising inhibitors of Axl/Mer for the treatment of cancer.

TAM（Axl，Mer和Tyro3）家族与肿瘤的存活和化学耐药有关，并已成为潜在的治疗靶标。一系列新型的7-芳基-2-苯胺基-吡咯并嘧啶被确认为有效的Axl / Mer酪氨酸激酶抑制剂，对Tyro3没有明显的抑制作用。代表性化合物27的IC _50为Mer和Axl的值分别为2 nM和16 nM，并且对细胞中的Mer磷酸化具有相当大的抑制作用。对接研究表明，在苯胺部分的氮与Mer激酶结构域的ASP678之间形成盐桥以及与大多数激酶抑制剂共同具有的铰链区相互作用对于保持活性至关重要。这些结果可为寻找有希望的Axl / Mer抑制剂用于治疗癌症提供有用的信息。