Scientists have found the inspiration for the newest cancer-fighting compound in the most peculiar of places: the tactics of the common cat burglar. In a recent study, researchers discovered a molecule capable of stopping the function of a common cancer regulator by unlatching its necessary interaction in a way very similar to how a cat burglar unlatches a lock with his credit card.
MYC is a cancer regulatory involved in gene expression. When MYC is overexpressed, the result is unregulated cell proliferation, a key step in cancer growth, according to a recent press release. For years, scientists have been attempting to halt this deadly reaction by targeting the MYC’s critical interactions with its binding partner. “We have been investigating this target off and on for close to 12 years and only finally have we gotten to a real success story,” co-author of the study, Dr. Kim Janda from The Scripps Research Institute, told Medical Daily via email. The success story Janda refers to is KJ-Pyr-9, a small molecule capable of effortlessly breaking this important link.
Researchers have struggled to find an effective method of targeting MYC because of its unique ever-changing structure. “It's like a piece of spaghetti," co-author Jonathon Ross Hart explained in the press release. “At room temperature or body temperature, MYC without any binding partners is random and constantly shifting."
KJ-Pyr-9 is what the team aptly dubbed a “credit card.” Like its namesake, the molecule carefully disrupts the cancerous interaction between MYC and other proteins needed for cell proliferation. During animal testing, a single dose of KJ-Pyr-9 made MYC appear almost nonexistent, and all cells that depended on the gene for survival subsequently died. For example, mice with tumors whose growth depended on MYC showed no signs of tumor growth after 31 days when treated with KJ-Pyr-9. Untreated mice continued to have significant cancer growth.
The researchers have big plans for this tiny molecule with big potentials. MYC is involved with around one in four cancers, which means that developing KJ-Pyr-9 into a drug could help countless people. In the future, it could be used for not only halting the further growth of cancer tumors, but actually completely ridding the body of cancer entirely.
At the moment, the compound is licensed to a company named Sorrento Therapeutics, but research on KJ-Pyr-9 is long from finished. “We will also seek funding to try and advance our understanding of its mechanism of action to make improved forms of the molecule,” Janda added.
Source: Janda KD, Hart JR, Garner AL, et al. Inhibitor of MYC identified in a Kröhnke pyridine library. Proceedings of the National Academy of Sciences of the United States of America. 2014.