Indolinyl-Thiazole Based Inhibitors of Scavenger Receptor-BI (SR-BI)-Mediated Lipid Transport
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Krieger_Indolinyl.pdf
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1.44 MB
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Author(s)
Dockendorff, Chris
Faloon, Patrick W.
Youngsaye, Willmen
Nag, Partha P.
Lewis, Timothy A.
Pu, Jun
Bennion, Melissa
Negri, Joseph
Paterson, Conor
Lam, Garrett
Date Issued
February 2015
Journal
ACS Medicinal Chemistry Letters
Publisher
American Chemical Society (ACS)
Citation
Dockendorff, Chris et al. “Indolinyl-Thiazole Based Inhibitors of Scavenger Receptor-BI (SR-BI)-Mediated Lipid Transport.” ACS Medicinal Chemistry Letters 6.4 (2015): 375–380. © 2015 American Chemical Society
Version
Final published version
Abstract
A potent class of indolinyl-thiazole based inhibitors of cellular lipid uptake mediated by scavenger receptor, class B, type I (SR-BI) was identified via a high-throughput screen of the National Institutes of Health Molecular Libraries Small Molecule Repository (NIH MLSMR) in an assay measuring the uptake of the fluorescent lipid DiI from HDL particles. This class of compounds is represented by ML278 (17–11), a potent (average IC[subscript 50] = 6 nM) and reversible inhibitor of lipid uptake via SR-BI. ML278 is a plasma-stable, noncytotoxic probe that exhibits moderate metabolic stability, thus displaying improved properties for in vitro and in vivo studies. Strikingly, ML278 and previously described inhibitors of lipid transport share the property of increasing the binding of HDL to SR-BI, rather than blocking it, suggesting there may be similarities in their mechanisms of action.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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DOI of Published Version
https://doi.org/10.1021/ml500154q
