NLRP3 is a receptor important for host responses to infection, yet is also known to contribute to devastating diseases such as Alzheimer's disease, diabetes, atherosclerosis, and others, making inhibitors for NLRP3 sought after. One of the inhibitors currently in use is 2-aminoethoxy diphenylborinate (2APB). Unfortunately, in addition to inhibiting NLRP3, 2APB also displays non-selective effects on cellular Ca2+ homeostasis. Here, we use 2APB as a chemical scaffold to build a series of inhibitors, the NBC series, which inhibit the NLRP3 inflammasome in vitro and in vivo without affecting Ca2+ homeostasis. The core chemical insight of this work is that the oxazaborine ring is a critical feature of the NBC series, and the main biological insight the use of NBC inhibitors led to was that NLRP3 inflammasome activation was independent of Ca2+. The NBC compounds represent useful tools to dissect NLRP3 function, and may lead to oxazaborine ring-containing therapeutics.
Pubmed ID: 28943355 RIS Download
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Portal for preclinical information and research materials, including web-accessible data and tools, NCI-60 Tumor Cell Line Screen, compounds in vials and plates, tumor cells, animals, and bulk drugs for investigational new drug (IND)-directed studies. DTP has been involved in the discovery or development of more than 70 percent of the anticancer therapeutics on the market today, and will continue helping the academic and private sectors to overcome various therapeutic development barriers, particularly through supporting high-risk projects and therapeutic development for rare cancers. Initially DTP made its drug discovery and development services and the results from the human tumor cell line assay publicly accessible to researchers worldwide. At first, the site offered in vitro human cell line data for a few thousand compounds and in vitro anti-HIV screening data for roughly 42,000 compounds. Today, visitors can find: * Downloadable in vitro human tumor cell line data for some 43,500 compounds and 15,000 natural product extracts * Results for 60,000 compounds evaluated in the yeast assay * In vivo animal model results for 30,000 compounds * 2-D and 3-D chemical structures for more than 200,000 compounds * Molecular target data, including characterizations for at least 1,200 targets, plus data from multiple cDNA microarray projects In addition to browsing DTP's databases and downloading data, researchers can request individual samples or sets of compounds on 96-well plates for research, or they can submit their own compounds for consideration for screening via DTP's online submission form. Once a compound is submitted for screening, researchers can follow its progress and retrieve data using a secure web interface. The NCI has collected information on almost half a million chemical structures in the past 50 years. DTP has made this information accessible and useful for investigators through its 3-D database, a collection of three-dimensional structures for more than 200,000 drugs. Investigators use the 3-D database to screen compounds for anticancer therapeutic activity. Also available on DTP's website are 127,000 connection tables for anticancer agents. A connection table is a convenient way of depicting molecular structures without relying on drawn chemical structures. As unique lists of atoms and their connections, the connection tables can be indexed and stored in computer databases where they can be used for patent searches, toxicology studies, and precursor searching, for example.
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View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis polyclonal targets Human IL-1 beta / IL-1F2
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View all literature mentionsCell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line Hep-G2 is a Cancer cell line with a species of origin Homo sapiens (Human)
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View all literature mentionsThis polyclonal targets Human IL-1 beta / IL-1F2
View all literature mentionsThis polyclonal targets Mouse IL-1 beta / IL-1F2
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