Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

TTR Fibril Formation Inhibitors: Is there a SAR?

Author(s): S. Nencetti, E. Orlandini

Volume 19 , Issue 15 , 2012

Page: [2356 - 2379] Pages: 24

DOI: 10.2174/092986712800269326

Price: $65

Abstract

Transthyretin is a homotetrameric protein that carries thyroxine and retinol binding protein in plasma and is associated with a variety of amyloid diseases. One approach to the potential treatment of TTR amyloidosis is the stabilization of the native tetramer, over the dissociative transition state, through the binding of small molecules; this increases the kinetic barrier for tetramer dissociation and prevents protein misfolding. Several molecules discovered through focused screening, or created utilizing the structure-based design, were studied to identify the structural features that could make up for a good candidate drug. In this review, we examine several different chemical classes of TTR fibril formation inhibitors, highlighting the structural modifications that have led to an improvement or to a decrease of their potency and/or selectivity.

Keywords: Transthyretin (TTR), TTR-amyloidosis, familial transthyretin amyloidosis (FAP, FAC, SSA), protein-misfolding disorders, TTR amyloid fibril formation inhibitors, structure based drug discovery, amyloid fibril formation inhibitors, SAR


Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy