Document Type

Article

Language

eng

Format of Original

6 p.

Publication Date

2015

Publisher

American Chemical Society

Source Publication

ACS Medicinal Chemistry Letters

Source ISSN

1948-5875

Original Item ID

DOI: 10.1021/ml500154q

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 (1711), a potent (average IC50 = 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.

Comments

Published version. ACS Medicinal Chemistry Letters, Vol. 6, No. 4 (2015): 375-380. DOI. © 2015 American Chemical Society. Used with permission.

ACS AuthorChoice - This is an open access article published under a Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.

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