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Members
Monash University hosts many of Australia’s premier research centers and institutions. Research at Monash...
The National University of Singapore (NUS) was founded in 1905 as a medical college. The Duke-NUS Medical...
Based on a tradition of global engagement, and creative approaches to education and research, Northeastern...
With its 18 interdisciplinary centers, cross-sector collaborative research is commonplace at Stanford. This...
Established in 1943, Swiss TPH conducts research on malaria, HIV, tuberculosis and other infectious diseases...
Researchers at UBC undertake a variety of research and development activities related to diseases of poverty,...
Collaborations
Drs. Meyers and Wildman were interested in the potential of PDE inhibitors to target a specific protein of interest in Mycobacterium tuberculosis (MTb). BVGH connected them with Dr. Pollastri, who had synthesized a set of PDE inhibitors as potential new drugs for HAT. Dr. Pollastri shared the structures of his compounds with Drs. Meyers and Wildman, who performed virtual docking studies to predict whether the inhibitors might have activity against MTb.
AstraZeneca scientists were interested in screening natural products for activity against M. tuberculosis. BVGH connected AstraZeneca with Dr. Quinn, who provided AstraZeneca with the GRIDD Nature Bank Fraction Library for their screening assays.
Cathepsins have been identified as potential drug targets across a range of infectious organisms. Drs. Caffrey, McKerrow, and Dr. Rosenthal were interested in screening cathepsin inhibitors against a selection of parasitic organisms. BVGH connected them with AstraZeneca, which provided cysteine protease inhibitors for screening against both human and parasitic enzyme targets.
Buruli ulcer, caused by Mycobacterium ulcerans, is a neglected tropical disease that, if left untreated, can cause debilitating skin ulcers and destruction of soft tissue. Current treatment involves eight weeks of antibiotics, a difficult course to implement in resource-limited settings. Drs. Pluschke and Scherr were interested in screening compounds against Buruli ulcer that had showed promise in screens against M. tuberculosis, as M. ulcerans is closely related to M. tuberculosis. BVGH facilitated a collaboration with AstraZeneca, which shared 100 anti-tuberculosis compounds (including one in clinical trials) for the Swiss TPH investigators to screen in their Buruli ulcer assay. While a number of potent antitubercular agents were only weakly active or inactive against M. ulcerans, five compounds showed high activity, making screening of focused antitubercular libraries a good starting point for lead generation against M. ulcerans.
Dr. Podust, an x-ray crystallographer, had been working on structure-based drug design for Chagas disease, and was interested in the potential of Cyp51 inhibitors. BVGH connected Dr. Podust with AstraZeneca, which shared 905 Cyp51 inhibitors. Dr. Podust’s collaborators, Drs. McKerrow and Siqueira-Neto, screened the compounds in high-throughput and cell-based assays against T. cruzi.
Key Personnel: Michael Pollastri (Northeastern University), Jean-Robert Ioset (DNDi), Byron Arana (DNDi), Marcel Kaiser (Swiss TPH). Dr. Pollastri had identified promising compounds in a screen against Leishmania major (the pathogen that causes cutaneous leishmaniasis). To support drug development efforts against additional neglected diseases, Dr. Pollastri shared his screening data with Drs. Arana and Ioset. With this data, Drs. Arana and Ioset connected with Dr. Kaiser, who screened the compounds for activity against Trypanosoma cruzi, T. brucei, L. donovani, and Plasmodium falciparum. Dr. Kaiser further conducted counter screens to assess cellular cytotoxicity.
Assets