Journal article
Combinatorial treatment of birinapant and zosuquidar enhances effective control of hbv replication in vivo
E Morrish, L Mackiewicz, N Silke, M Pellegrini, J Silke, G Brumatti, G Ebert
Viruses | MDPI | Published : 2020
DOI: 10.3390/v12080901
Abstract
Chronic hepatitis B virus (HBV) infection remains a global health threat and affects hundreds of millions worldwide. Small molecule compounds that mimic natural antagonists of inhibitor of apoptosis (IAP) proteins, known as Smac-mimetics (second mitochondria-derived activator of caspases-mimetics), can promote the death of HBV-replicating liver cells and promote clearance of infection in preclinical models of HBV infection. The Smac-mimetic birinapant is a substrate of the multidrug resistance protein 1 (MDR1) efflux pump, and therefore inhibitors of MDR1 increase intracellular concentration of birinapant in MDR1 expressing cells. Liver cells are known to express MDR1 and other drug pump pro..
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Awarded by Leukemia and Lymphoma Society
Funding Acknowledgements
This work was supported by the Leukemia & Lymphoma Society SCOR (Specialized Centre of Research, grant #7015-18 to JS); the Cancer Australia and Leukaemia Foundation Australia (priority grant PdCCRS 1162023 to G.B.); the Australian National Health and Medical Research Council, NHMRC (grants 1025594, 1046010 (J.S.), 1081376 (G.B. and J.S.) and 1065626 (M.P.)); and NHMRC fellowship (1058190 to J.S.); and a Victoria Cancer Agency (VCA) mid-career fellowship (MCRF 15027 to G.B.). This work was made possible through the Australian Cancer Research Foundation, the Victorian State Government Operational Infrastructure Support; and the Independent Research Institutes Infrastructure Support Scheme of the Australian Government NHMRC and Australian Government NHMRC IRIISS (9000433).