Nurix is pioneering rational drug design in the emerging field of protein regulation by targeting E2 conjugating enzymes and E3 ligases that control the Ubiquitin Proteasome System (UPS).
Regulation of protein stability by the UPS is modulated by the activity of these E2 and E3 enzymes, which control the tagging of proteins with ubiquitin for degradation by the proteasome. The human genome encodes approximately 1,000 different E3 ligases and 60 E2 enzymes. A number of these ligases recently have been shown to play key roles in human diseases, particularly in cancer and autoimmune disease.
Although discovered prior to scientific understanding of the central role of the UPS in cellular metabolism, highly successful drugs such as Velcade®, Kyprolis® and Revlimid® have been found to act through modulation of the UPS. Velcade® and Kyprolis® are 26S proteasome inhibitors and Revlimid® is a modulator of cereblon, an E3 ligase. And yet, notably, these products target only two of the multitude of UPS pathways now available for drug discovery.
Nurix’s Protein Regulation Platform unlocks the E3 and E2 enzyme class of targets for important medical breakthroughs by using a combination of proprietary screens, insights from structural biology, and our unique Molecular Glue chemistry to develop a class-wide drug discovery advantage.
John Kuriyan and Michael Rape