SIRT3

New business unit is focused on "undruggable" targets for age-related indications and genetically inherited diseases. MOUNT LAUREL, N.J., Sept. 20, 2023 /PRNewswire/ -- CCM Biosciences, a pharmaceutical discovery and development company that recently confirmed its launch from stealth, today announced its latest business unit — CCM Protein Upregulation — dedicated to advancing first-in-class drug leads for age-related conditions such as Alzheimer's, Parkinson's, and infertility as well as for genetically inherited diseases such as cystic fibrosis, using highly differentiated technology platforms for improving the enzymatic activity or expression level of critical proteins implicated in the pathogenesis of such disorders. Continue Reading Enhancement of the activity or expression level of proteins is important for the treatment of many age-related and genetically inherited conditions. However, whereas reduction of enzymatic activity or protein expression level can be achieved for a very broad class of protein targets by inhibitors — which comprise the vast majority of small molecule drugs — and protein degraders, respectively, enhancement of the activity or expression level of protein targets is notoriously difficult. Protein targets susceptible to enzymatic activity enhancement have historically been almost entirely restricted to those with naturally evolved, so-called allosteric binding sites, and enhancement of protein expression by orally bioavailable drug molecules generally requires interaction between the drug and the cellular machinery for protein synthesis at the genetic level. CCM Protein Upregulation's technology platform is comprised of methods for the design of drugs that can enhance enzyme activity in the absence of allosteric binding sites, as well as drugs that can enhance translation of messenger RNAs (mRNAs) for genes bearing nonsense mutations to enable efficient production of functional proteins. CCM's sirtuin-activating drug leads were discovered in-house using its proprietary, patented drug discovery platform. Tweet this Advances aimed at improving human healthspan and lifespan are arguably among the most coveted targets in healthcare but also among the most scientifically complex ones. A class of enzymes known as sirtuins has been shown to play a central role in the regulation of human longevity and age-related diseases. However, most of these enzymes are considered "undruggable" because of the challenge of improving the activity of these enzymes in the absence of known allosteric sites. Among the seven mammalian sirtuin enzymes SIRT1-7, only SIRT1 has a known allosteric site. To date, sirtuin activation has been pursued pharmaceutically for SIRT1 by allosteric activation and for other sirtuins by nutraceutical supplements that are not drugs. CCM's sirtuin-activating drug leads were discovered in-house using its proprietary, patented drug discovery platform, which combines computational biophysics and DNA-Encoded Libraries, building upon publications by CCM scientists in the Proceedings of the National Academy of Sciences, Bioorganic and Medicinal Chemistry, the Journal of Chemical Physics, and PLoS. Application of the platform led to the discovery of novel first-in-class hits for activation of SIRT3, the major sirtuin enzyme in mitochondria – the energy production powerhouses of cellular metabolism that become less efficient with age, in part due to loss of sirtuin activity. "Characterization of the novel sirtuin activators uncovered for the first time the mechanism whereby they can activate enzymes without allosteric sites. In particular, these compounds were shown to increase up to two-fold the catalytic efficiency of SIRT3 under conditions wherein the essential metabolic cofactor NAD+ is depleted, as it is in old age. Such compounds have the potential to rejuvenate the activity of SIRT3 to levels observed in youth," said Dr. Raj Chakrabarti, CEO of CCM Biosciences. Preclinical studies are underway on evaluating the efficacy of such non-allosteric sirtuin activators for conditions stemming from the decline of mitochondrial function and NAD+ levels with age, such as Parkinson's and the reduction of fertility in females of advanced maternal age. Genetically inherited diseases affect hundreds of millions of people worldwide. An estimated 30 million of those patients are impacted by a nonsense mutation, which results in making an incomplete, nonfunctional protein product. CCM Protein Upregulation's drug leads represent a first-in-class opportunity to treat multiple diseases caused by nonsense mutations. The company's drug leads for nonsense mutation translational readthrough were discovered using computer-aided drug discovery methods, and acquired through exclusive licensing rights from the University of Palermo and the Italian Cystic Fibrosis Foundation. With promising preclinical animal study results, IND-enabling studies for the lead indication of cystic fibrosis are underway. About CCM Biosciences CCM Biosciences is a biotechnology company dedicated to discovering and developing novel drugs, including small molecules, gene therapies, biologics, and nanomedicines. CCM's patented drug discovery platforms were developed at Chakrabarti Advanced Technology, a privately funded R&D institute founded in 2010 with scientists in the US, France and India and with publications in leading scientific journals including PNAS, Nucleic Acids Research, American Chemical Society journals and Nature Publishing Group journals. These platforms are complemented by the contract research, development, and manufacturing organizations (CRDMO) at PMC Group, developed through acquisitions of industry-leading companies. Contact: Anisha Ghosh Email: [email protected] SOURCE CCM Biosciences