Drugging the Ral GTPase.
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.
a Departments of Surgery (Urology) and Pharmacology ; University of Colorado ; Aurora , CO USA.
Chao
C
Yan
David N M
DN
Jones
Dan
D
Theodorescu
D000495:Allosteric Site; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols; D045744:Cell Line, Tumor; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D015398:Signal Transduction / Q000187:drug effects; D054852:Small Molecule Libraries / Q000378:metabolism / Q000494:pharmacology*; D020725:ral GTP-Binding Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D018631:ras Proteins / Q000037:antagonists & inhibitors
D000970:Antineoplastic Agents; D054852:Small Molecule Libraries; D020725:ral GTP-Binding Proteins; D018631:ras Proteins
GTPase; Ral; Ras; allosteric; metastasis; personalized medicine; precision medicine; small molecule; targeted therapy