Journal article
A novel small molecule inhibitor of human Drp1
AA Rosdah, BM Abbott, CG Langendorf, Y Deng, JQ Truong, HMM Waddell, NXY Ling, WJ Smiles, LMD Delbridge, GS Liu, JS Oakhill, SY Lim, JK Holien
Scientific Reports | NATURE PORTFOLIO | Published : 2022
Open access
Abstract
Mitochondrial dynamin-related protein 1 (Drp1) is a large GTPase regulator of mitochondrial dynamics and is known to play an important role in numerous pathophysiological processes. Despite being the most widely used Drp1 inhibitor, the specificity of Mdivi-1 towards human Drp1 has not been definitively proven and there have been numerous issues reported with its use including off-target effects. In our hands Mdivi-1 showed varying binding affinities toward human Drp1, potentially impacted by compound aggregation. Herein, we sought to identify a novel small molecule inhibitor of Drp1. From an initial virtual screening, we identified DRP1i27 as a compound which directly bound to the human iso..
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Awarded by Jack Brockhoff Foundation
Funding Acknowledgements
This work was supported by grants from the St Vincent's Hospital (Melbourne) Research Endowment Fun, Stafford Fox Medical Research Foundation and infrastructure funding from the Victorian Government (Australia) Operational Infrastructure Support Scheme to St. Vincent's Institute of Medical Research. A.A.R. is supported by Australia Awards Scholarship. J.K.H. is supported by an RMIT Vice Chancellors Fellowship and was previously supported by a 5Point Foundation Fellowship. N.X.Y.L. and J.S.O. are supported by an Australian Research Council (A.R.C.) grant DP220103700. This work was supported by grants from the Jack Brockhoff Foundation (no. JBF-4206 to C.G.L.). C.G.L. is an NHMRC Early Career Research Fellow and was previously supported by a EH Flack fellowship.