Sirtuin Platform

At Sirtris, our focus is on the sirtuins, a family of seven NAD⁺-dependent enzymes several of which have been characterized as protein deacetylases and associated with cellular energetics and stress responses. The discovery of the first human sirtuin, SIRT1 resulted from research into the health benefits and life extension seen in multiple species on calorie-restricted diets. Rats, mice, and non-human primates on calorie-restricted diets are healthier (improved healthspan) and live longer.

Calorie restriction, as well as other metabolic stress responses have been shown to impact multiple cellular signaling pathways — many of which can be linked to an increase in the SIRT1-mediated deacetylation of multiple cellular substrates. Our goal is to mimic the beneficial effects of calorie restriction by developing small molecule activators that biochemically increase the catalytic activity of SIRT1.

Preclinical studies with SIRT1 activators have demonstrated potential importance in multiple disease areas, including Type 2 diabetes and related complications, cardiovascular, inflammatory and neurodegenerative diseases.

While SIRT1 was the first in this family of enzymes to be discovered, considerable research is also under way on other members in this family, SIRTs 2-7. In particular, SIRT3, another broad specificity protein deacetylase, has emerged as a critical member of the family that has been firmly implicated in regulating cellular energetics in times of stress and, more recently, as a possible key player in cancer metabolism. The involvement of the sirtuins in a variety of disease pathways suggests that the family represents an attractive portfolio of potential drug targets.

+Potential Disease Area Applications

Sirtris' discovery efforts benefit from integrated teams focused on sirtuin biology, medicinal chemistry, clinical and translational medicine, and drug product process development and formulation. We have also formed important research partnerships with investigators in the academic community as well as other groups within GSK, sharing sirtuin modulators to develop new disease pathway knowledge. If you would like to partner with Sirtris in a research collaboration, please email Dr. Jennifer Cermak at: jennifer.5.cermak@gsk.com.