The term “epigenetic” describes a process capable of altering gene expression without affecting the underlying gene sequence. Such activity is typically orchestrated by the binding of certain chemical mediators to a cell’s DNA or to DNA-related structural proteins called histones.
Epigenetic mechanisms play a role in regulating many important cellular functions, from simple protein synthesis to large-scale phenotypic shifts such as cell differentiation. Substances that can epigenetically influence gene expression may hold substantial therapeutic promise and are the basis of active drug development at DURECT.
DURECT's Epigenetic Regulator Program is a collaborative effort between DURECT and the Department of Internal Medicine at Virginia Commonwealth University (VCU), the VCU Medical Center and the McGuire VA Medical Center. The program capitalizes on more than 20 years of research by Shunlin Ren, M.D., Ph.D., Professor of Internal Medicine at the VCU Medical Center and a recipient of multiple grants from the National Institutes of Health (NIH) for metabolic disease research.
The program builds on the recent discovery of a family of epigenetically-active endogenous small molecules that may have therapeutic utility in a wide range of diseases and syndromes—both orphan in nature and affecting broader patient populations. DUR-928, the lead compound in this program, appears to be highly conserved across species. Nonclinical studies have shown it to modulate the activity of several nuclear receptors and to play a key regulatory role in lipid homeostasis, inflammation, and cell survival.
Compelling animal data derived from 10 disease models involving 3 animal species—predominantly in acute organ injury and metabolic dysregulation—suggest potential therapeutic effects in humans, and these findings are shaping DURECT’s clinical development strategy for DUR-928.
Learn more about our Epigenetic Regulator Program lead product candidate: