Applying a newly identified biophysical mechanism of enzyme activation, researchers at the longevity therapeutics division of the diversified biopharmaceutical company CCM Biosciences, Inc., have discovered and characterized first-in-class enzyme activators for a previously undruggable master regulator of cellular energy production. These first-in-class compounds fully restore the enzyme’s activity to youthful levels and hold significant potential for clinical development to address a range of age-related disorders, including Alzheimer’s, Parkinson’s, cardiovascular conditions, and metabolic diseases.
Finding enzyme-activating compounds has historically been challenging because they typically rely on a mechanism called allosteric modulation, which is feasible in less than 10% of proteins. Recently, researchers at CCM Biosciences and its affiliated R&D center Chakrabarti Advanced Technology expanded the scope of enzyme activation beyond allosteric modulation by introducing novel physical principles for enzyme activation. Using these principles, they applied computational and experimental design techniques to identify compounds that drastically enhance the activity of the previously undruggable enzyme Sirtuin-3 (SIRT3), which is centrally involved in regulating human aging. This study was published in Physical Review X, the flagship journal of the American Physical Society (APS), on 22 October 2024.
https://journals.aps.org/prx/abstract/10.1103/PhysRevX.14.041019
