A growing team of groundbreaking scientists around the world are now sharing their lab notebooks online
High throughput screening (HTS) is a powerful technique for identifying potential drug candidates from large libraries of compounds. However, many compounds that show activity in HTS are false positives or may not be suitable for further development. Therefore, it is important to apply various filters to eliminate compounds that have undesirable properties, such as poor Read More …
by Mohammad Anwar Hossain1, Konstantin Popov2, Sumera Perveen3, Kesatebrhan Haile Asressu1, Kenneth Hugh Pearce Jr.2, Cheryl Arrowsmith3, Peter Brown1, Alexander Tropsha4, Tim Willson1 1Structural Genomics Consortium, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 2CICBDD, UNC Eshelman School of Pharmacy; 3The Structural Genomics Consortium, University of Toronto, Canada; 4CBMC, UNC Eshelman Read More …
Introduction Situation Kinases are useful for drug discovery – many opportunities! Kinase by kinase probe development is important, but it will take too long to discover a probe for each kinase Disease relevant phenotypic assays need smart compounds sets Numerous high quality kinase inhibitors exist in the literature and in company collections Kinases are “connected” Read More …
SARS-CoV-2 Helicase (NSP13) as a drug target: The pandemic caused by SARS-CoV-2 is not over yet but instead has transformed into a chronic illness. So far, the expedited effort on drug development produced Mpro targeting drugs (Paxlovid) and repurposed RdRp inhibitor Molnupiravir. For effective long-term treatment, we intend to discover complementary antivirals targeting replication machinery Read More …
In searching for novel drugs that will treat future viral pandemics, the AViDD program has prioritized viral proteases, helicases, and RNA-dependant RNA polymerases (RdRps) as key targets in the fight to control viral replication. At the time of writing, several drugs are either in the clinic or on the market for SARS-CoV-2 proteases and RdRps, Read More …
Introduction: The outbreak of COVID-19 demonstrated the scarcity of drugs in the development pipeline to decrease the mortality and morbidity caused by the new pathogenic SARS-CoV-2 virus. Despite the improved diagnosis and screening processes, broad directly-acting anticoronavirus drugs were not immediately available to treat viral infections. In response to this health threat, the Rapidly Emerging Read More …
In this blog post, I will discuss the progress made on improving the binding affinity of new covalent quinazolines targeting CYS122, as well as some of the directions we are taking to further improve binding affinity to TBXT and reduce binding affinity towards EGFR. The synthetic work has been primarily driven by Zach and our Read More …
Our chordoma research focused on developing small reversible molecules targeting the transcription factor TBXT which codes for the brachyury protein. Brachyury contains several shallow pockets, and through an x-ray crystallography fragment based approach we previously identified several series of small fragments bound to it (TBXT Fragment Hits). Our medicinal chemistry project aimed to grow the Read More …
By Zachary Davis-Gilbert, Anwar Hossain, and David H. Drewry* In conjunction with our efforts to target TBXT via non-covalent small molecules, we have also been developing covalent compounds that bind to CYS122, which has previously been shown to be accessible by afatinib (pdb code 6ZU8). In this blog post, I will discuss the progress made Read More …
This week we released our Surface Plasmon Resonance (SPR) data for the binding of small molecules to brachyury (gene name TBXT) on Zenodo (https://doi.org/10.5281/zenodo.6394811). The raw data was collected by HD Biosciences as part of an ongoing campaign to identify potent ligands of this transcription factor that is critically important to chordoma cells. This upload Read More …
