Drugging the Ral GTPase

Abstract

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.

Keywords:

• allosteric
• GTPase
• metastasis
• personalized medicine
• precision medicine
• Ral
• Ras
• small molecule
• targeted therapy

This article refers to:

Funding

This work was supported in part by NIH grant CA091846.

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.