
The Myc protein has also been recognized as an important determinant of cancer metabolism and protein synthesis. It is involved as a dominant factor in most human cancers and is rarely mutated, but rather its “gain of function” results from overexpression or gene amplification. Abnormal Myc activity is believed to play a substantial role in at least one out of every seven cancer deaths and is often a key factor in breast, lung, colon, hematologic, and other cancers.
Recent work on Myc highlighted the unexpected roles in cancers of nominally non-Myc etiology, such as KRAS-driven lung cancer, and also cellular resistance to PI3K inhibitors might be mediated by Myc activity. However, potent and selective small molecule Myc inhibitors have been very difficult to identify due to the structural characteristics of the Myc molecule.
Sorrento was awarded a Phase 1 Small Business Technology Transfer Research (STTR) grant from the National Cancer Institute (NCI), a division of the National Institutes of Health (NIH), which will support the preclinical development of the Myc inhibitor, which interferes with the protein-protein interaction (PPI) between Myc and its obligatory dimerization partner, Max, preventing sequence-specific binding to DNA and subsequent initiation of oncogenic transformation.
The principal investigator on the STTR grant is Sorrento’s Senior Director of Research and Development Dr. Gunnar Kaufmann, and the academic collaborator is Dr. Kim Janda at The Scripps Research Institute (TSRI), a world-renowned chemical biologist and expert in PPI inhibitors. Earlier this year, Sorrento obtained an exclusive license from TSRI to the Myc inhibitors, the scientific foundation for this program.
Dr. Peter Vogt, EVP, CSO, & professor at TSRI, co-discoverer of the Myc, jun, PI3K, & src oncogenes, and Sorrento’s collaborator on this project, noted that “Myc has also been called the ’emperor of oncogenes.’ Targeting Myc with a small molecule inhibitor has been a daunting challenge and has given rise to the current dogma that Myc is ‘undruggable.’ Numerous studies have strengthened Myc’s candidacy as a promising cancer drug target and also suggest that Myc inhibition might be therapeutic in many or most cancer types, irrespective of the underlying driving oncogenic mechanism. This clearly enhances the significance and importance of this potential scientific breakthrough.”
The scientific details of these Myc inhibitors will be published in a forthcoming manuscript submitted by Dr. Janda, Vogt and their TSRI colleagues.
“While Sorrento’s focus will remain on developing our clinical stage assets Cynviloq and resiniferatoxin (RTX) as quickly and efficiently as possible, government-sponsored research allows us to explore innovative anti-cancer strategies, such as this potentially first-in-class Myc inhibitor. Our academic collaborators at TSRI and Sorrento’s research team will perform the preclinical studies needed to bring this program to an inflection point. We are very grateful for NCI’s support of this exciting and potentially paradigm-shifting program,” said Henry Ji, president and CEO of Sorrento.
Date: July 21, 2014
Source: Sorrento Therapeutics
Filed Under: Drug Discovery