Writing in the Proceedings of the National Academy of Sciences (PNAS) Professors Kim D. Janda and Peter K. Vogt, a research team at The Scripps Research Institute (TSRI) reported that the function of the MYC regulator could be inhibited with small molecule compounds in cell culture and importantly in an experimental cancer animal model.[1]
The MYC protein is a transcriptional factor. This means that it controls gene expression. The MYC protein has 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 functionresults from overexpression or gene amplification. Abnormal MYC activity is believed to be a key factor in breast, lung, colon, hematologic and other cancers, including Burkitt’s lymphoma, a fast-growing cancer that tends to strike children.
Targeting MYC with a small molecule inhibitor has been a daunting challenge and has given rise to the current dogma that MYC is undruggable
Small molecule MYC inhibitors interfere with the protein-protein interaction or PPI between MYC and its obligatory dimerization partner, Max, preventing sequence-specific binding to DNA and subsequent initiation of oncogenic transformation. The unregulated expression of genes involved in cell proliferation, a key step in cancer growth, follows.
Phase I development
Sorrento Therapeutics, Inc., a late-stage clinical oncology company developing new treatments for cancer and its associated pain, licenses the MYC inhibitors from The Scripps Research Institute. On July 21, 2014, the company announced that preclinical development of a MYC inhibitor would be supported by a Phase I Small Business Technology Transfer Research (STTR) grant received from the National Cancer Institute (NCI), a division of the National Institutes of Health (NIH).
Professor Vogt, who is the 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.”
Unsuccessfully pursued
“Based on its dominant role in multiple forms of cancer, it is widely acknowledged that MYC is a very important but yet unsuccessfully pursued target for cancer therapy. We are excited to have these potent and unique inhibitors in our development portfolio,” said Henry Ji, Ph.D., President and Chief Executive Officer of Sorrento. “In addition, the funding from the NCI STTR grant will allow us to dedicate research support without diverting resources from other programs in our pipeline, such as the clinical development activities for Cynviloq?, paclitaxel polymeric micelle for injection, a novel nanoparticle formulation of paclitaxel, and RTX.”
For more information:
[1] Hart JR, Garner AL, Yu J, Ito Y, Sun M, Ueno L, Rhee JK. Inhibitor of MYC identified in a Kr?hnke pyridine library. Proc Natl Acad Sci U S A. 2014 Aug 11. pii: 201319488. [Article][PubMed]
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