alexa An In vitro Cell-Based LDL Uptake Model for Screening PCSK9 Modulators | OMICS International | Abstract
ISSN: 0975-0851

Journal of Bioequivalence & Bioavailability
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Research Article

An In vitro Cell-Based LDL Uptake Model for Screening PCSK9 Modulators

Weiming Xu1,2* and Lizhi Liu1,2

1Department of Molecular Biology and Biotechnology, University of Sheffield, S10 2TN, UK

2London Biotech Ltd, 19 Crawley Road, London, N22 6AN, UK

*Corresponding Author:
Weiming Xu
Department of Molecular Biology and Biotechnology
University of Sheffield, S10 2TN, UK
Tel: 0114 2222 785
E-mail: [email protected]

Received Date: October 25, 2013; Accepted Date: November 27, 2013; Published Date: December 04, 2013

Citation: Xu W, Liu L (2013) An In vitro Cell-Based LDL Uptake Model for Screening PCSK9 Modulators. J Bioequiv Availab 5:248-252. doi: 10.4172/jbb.1000168

Copyright: © 2013 Xu W, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

PCSK9 plays a critical role in cholesterol metabolism by controlling the level of low-density lipoprotein receptor(LDLR). Recent population genetic studies have shown that PCSK9 is a genetic validated target for the reduction of LDLc. Several anti-PCSK9 antibodies are currently undergoing Phase II/III trails in patients with hypercholesterolemia with promising results. However, developing novel compounds that inhibit PCSK9 function is pharmaceutically preferred over both antibody and siRNA routes. We have recently developed a cell-based, functional assay incorporating recombinant PCSK9 protein for high-throughput screening of human liver cell HepG2. A pilot screen of the NINDS compound library has been successful in identifyng several potential compounds in duplicate screening. One of the lead compounds, colchicine, has been further validated with the Western blot assay for PCSK9-mediated LDLR degradation in dose-reponsive assay. Colchicine is a prescribing drug for the treatment of acute gout flares and familial Mediterranean fever. Identification of colchicine as a modulator of PCSK9 function highlights the potential of the novel use of this drug for cardiovascular disease treatment.

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