New insights into the structure and mechanism of these proteins may be essential for development of novel disease treatments
WALTHAM, Mass. & MONTREAL, January 6, 2022 – Ventus Therapeutics U.S., Inc., a biopharmaceutical company utilizing structural biology and computational tools to identify and develop small molecule therapeutics across a broad range of disease indications, today announced a publication in the peer-reviewed journal Journal of Experimental Medicine entitled “Advances toward structure-based drug discovery for inflammasome targets.” (Wang et al., J Exp Med. 2022 Jan 3;219(1):e20211147)
The article summarizes the historic difficulties of targeting inflammasome proteins for the treatment of several diseases of high unmet need, and how advances in structural biology could overcome these challenges. The authors describe the generation of increasingly high-resolution crystal structures, including a 2.6 angstrom-resolution structure of monomeric NLRP3, an inflammasome protein that is the focus of many development efforts in academia and industry.
“We believe recent advances in our understanding of the structure and mechanisms of key inflammasome proteins such as NLRP3 offer tremendous insight into inflammasome signaling, paving the way for structure-based drug design,” said Li Wang, PhD, lead author on this article and Principal Scientist at Ventus.
“Having a more precise view of inflammasome proteins may further unlock the possibilities of developing novel therapeutics for a range of conditions including autoimmune and inflammatory diseases and neurological disorders,” said Michael Crackower, PhD, Chief Scientific Officer of Ventus.
NLRP3 (NLR pyrin domain-containing 3) is a member of a family of proteins known as inflammasome receptors and is integral in the formation of the NLRP3 inflammasome. Inflammasomes are multiprotein complexes that regulate the innate immune system and are involved in intracellular surveillance of danger signals that trigger an intense inflammatory response, via generation of IL-1β, IL-18 and lytic cell death termed as pyroptosis. Therapeutic inhibition of NLRP3 can, therefore, prevent the formation of the NLRP3 inflammasome, which in turn inhibits the production of IL-1β and IL-18. Aberrant activation of the NLRP3 inflammasome has been associated with systemic conditions including fibrotic, dermatological and rheumatological diseases and figures prominently in several neurological disorders including Alzheimer’s disease, Parkinson’s disease and multiple sclerosis.
About Ventus Therapeutics
Ventus Therapeutics is a biopharmaceutical company utilizing structural biology and computational tools to identify and develop small molecule therapeutics across a broad range of disease indications, with an initial focus on immunology, inflammation and neurology. We have developed a proprietary drug discovery platform, called ReSOLVE, which is built upon our structural biology and protein science expertise and our proprietary computational chemistry capabilities, to address the current limitations of small molecule drug discovery. We are leveraging our ReSOLVE platform to discover and characterize previously unknown or poorly understood pockets on the surface of proteins and identify small molecules that can bind to those pockets with optimal affinity. We are focused on high-value targets that have been extensively implicated in human diseases that were previously considered undruggable or where we believe there is a significant opportunity to improve upon existing therapies. Our lead programs target key innate immune modulators, including NLRP3 and cGAS. For more information, please visit www.ventustx.com and engage with us on Twitter @Ventus_Tx or on LinkedIn.
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