Yan Chao, Jones David N M, Theodorescu Dan
a Departments of Surgery (Urology) and Pharmacology ; University of Colorado ; Aurora , CO USA.
Small GTPases. 2015;6(3):157-9. doi: 10.1080/21541248.2015.1018403.
The RAL GTPases have emerged as important drivers of tumor growth and metastasis in lung, colon, pancreatic and other cancers. We recently developed the first small molecule inhibitors of RAL that exhibited antitumor activity in human lung cancer cell lines. These compounds are non-competitive inhibitors that bind to the allosteric site of GDP-bound RAL. The RAL inhibitors have the potential to be used in combination therapy with other inhibitors of the RAS signaling pathway. They also provide insights toward directly targeting other GTPases.
RAL GTP酶已成为肺癌、结肠癌、胰腺癌和其他癌症中肿瘤生长和转移的重要驱动因素。我们最近开发了首批RAL小分子抑制剂，这些抑制剂在人肺癌细胞系中表现出抗肿瘤活性。这些化合物是非竞争性抑制剂，可与结合GDP的RAL的变构位点结合。RAL抑制剂有潜力与RAS信号通路的其他抑制剂联合使用。它们还为直接靶向其他GTP酶提供了思路。
