Journal article

Combinatorial Treatment of Birinapant and Zosuquidar Enhances Effective Control of HBV Replication In Vivo

Emma Morrish, Liana Mackiewicz, Natasha Silke, Marc Pellegrini, John Silke, Gabriela Brumatti, Gregor Ebert

VIRUSES-BASEL | MDPI | Published : 2020

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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Grants

Awarded by Leukemia & Lymphoma Society SCOR (Specialized Centre of Research)


Awarded by Leukaemia Foundation Australia


Awarded by Australian National Health and Medical Research Council, NHMRC


Awarded by NHMRC


Awarded by Victoria Cancer Agency (VCA) mid-career fellowship


Awarded by Independent Research Institutes Infrastructure Support Scheme of the Australian Government NHMRC


Awarded by Australian Government NHMRC IRIISS


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).