Journal ArticleDOI
Inhibitors of BACE for treating Alzheimer's disease: a fragment-based drug discovery story.
Andrew Stamford,Corey Strickland +1 more
Reads0
Chats0
TLDR
In this paper, a non-planar cyclic amidine motif with a phenyl group projecting into S1 was identified as a key pharmacophore for BACE1 inhibitors.About:
This article is published in Current Opinion in Chemical Biology.The article was published on 2013-06-01. It has received 64 citations till now. The article focuses on the topics: Pharmacophore & Fragment-based lead discovery.read more
Citations
More filters
Journal ArticleDOI
Data-mining for sulfur and fluorine: an evaluation of pharmaceuticals to reveal opportunities for drug design and discovery.
TL;DR: The evolution and structural diversity of sulfur and the popular integration of fluorine into drugs introduced over the past 50 years are evaluated and promoted to promote innovative insights into drug development.
Journal ArticleDOI
Function, therapeutic potential and cell biology of BACE proteases: current status and future prospects.
Robert Vassar,Peer-Hendrik Kuhn,Peer-Hendrik Kuhn,Christian Haass,Christian Haass,Matthew E. Kennedy,Matthew E. Kennedy,Lawrence Rajendran,Philip C. Wong,Stefan F. Lichtenthaler +9 more
TL;DR: This review highlights the recent progress in understanding cell biology, substrates, and functions of BACE proteases and discusses the therapeutic options and potential mechanism‐based liabilities, in particular for BACE inhibitors in Alzheimer's disease.
Journal Article
[Discovering high-affinity ligands for proteins: SAR by NMR].
Shinji Kamisuki,Motonari Uesugi +1 more
Journal ArticleDOI
Amyloid cascade in Alzheimer's disease: Recent advances in medicinal chemistry
TL;DR: This work demonstrates that the structural requirements to prevent aggregation of various amyloid species differs considerably, which explains the fact that many small molecules do not exhibit similar inhibition profile toward diverse amyloids species such as dimers, trimers, tetramers, oligomers, protofibrils and fibrils.
References
More filters
Journal ArticleDOI
The Amyloid Hypothesis of Alzheimer's Disease: Progress and Problems on the Road to Therapeutics
John Hardy,Dennis J. Selkoe +1 more
TL;DR: It has been more than 10 years since it was first proposed that the neurodegeneration in Alzheimer's disease (AD) may be caused by deposition of amyloid β-peptide in plaques in brain tissue and the rest of the disease process is proposed to result from an imbalance between Aβ production and Aβ clearance.
Journal ArticleDOI
Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE.
Robert Vassar,Brian D. Bennett,Safura Babu-Khan,Steve Kahn,Elizabeth A. Mendiaz,Paul Denis,David B. Teplow,Sandra Ross,Patricia Amarante,Richard Loeloff,Yi Luo,Seth Fisher,Janis Fuller,Steven P. Edenson,Jackson Lile,Mark A. Jarosinski,Anja Leona Biere,Eileen Curran,Teresa L. Burgess,Jean Claude Louis,Frank H. Collins,James J. S. Treanor,Gary Rogers,Martin Citron +23 more
TL;DR: Overexpression of a transmembrane aspartic protease, termed BACE (for beta-site APP-cleaving enzyme) increased the amount of beta-secretase cleavage products, and these were cleaved exactly and only at known beta- secretase positions.
Journal ArticleDOI
Discovering High-Affinity Ligands for Proteins: SAR by NMR
TL;DR: A nuclear magnetic resonance (NMR)-based method is described in which small organic molecules that bind to proximal subsites of a protein are identified, optimized, and linked together to produce high-affinity ligands and appears particularly useful in target-directed drug research.
Journal ArticleDOI
The amyloid cascade hypothesis for Alzheimer's disease: an appraisal for the development of therapeutics.
TL;DR: It is timely to review the science underpinning the amyloid cascade hypothesis, consider what type of clinical trials will constitute a valid test of this hypothesis and explore whether amyloids-β-directed therapeutics will provide the medicines that are urgently needed by society for treating this devastating disease.
Journal ArticleDOI
Purification and cloning of amyloid precursor protein beta-secretase from human brain.
Sukanto Sinha,John P. Anderson,Robin Barbour,Guriqbal S. Basi,Russell J. Caccavello,David Davis,Minhtam Doan,Harry F. Dovey,Normand Frigon,Jin Hong,Kirsten L. Jacobson-Croak,Nancy Jewett,Pamela S. Keim,J. Knops,Ivan Lieberburg,Michael Power,Hua Tan,Gwen Tatsuno,Jay Tung,Dale Schenk,Peter Seubert,Susanna Suomensaari,Shuwen Wang,Donald A. Walker,Jun Zhao,Lisa McConlogue,Varghese John +26 more
TL;DR: A membrane-bound enzyme activity that cleaves full-length APP at the β-secretase cleavage site is described and found to be the predominant β-cleavage activity in human brain, and it is found that human brain β- secretase is a new membrane- bound aspartic proteinase.
Related Papers (5)
Robust Central Reduction of Amyloid-β in Humans with an Orally Available, Non-Peptidic β-Secretase Inhibitor
Patrick C. May,Robert A. Dean,Stephen L. Lowe,Ferenc Martenyi,Scott Martin Sheehan,Leonard N. Boggs,Scott A. Monk,Brian Michael Mathes,Dustin J. Mergott,Brian Morgan Watson,Stephanie L. Stout,David E. Timm,E. Smith LaBell,Celedon Gonzales,M. Nakano,Stanford Jhee,Mark Yen,Larry Ereshefsky,Terry D. Lindstrom,David O. Calligaro,Patrick J Cocke,D. Greg Hall,Stuart Friedrich,Martin Citron,James E. Audia +24 more
The Amyloid Hypothesis of Alzheimer's Disease: Progress and Problems on the Road to Therapeutics
John Hardy,Dennis J. Selkoe +1 more
A mutation in APP protects against Alzheimer’s disease and age-related cognitive decline
Thorlakur Jonsson,Jasvinder K. Atwal,Stacy Steinberg,Jon Snaedal,Palmi V. Jonsson,Sigurbjorn Bjornsson,Hreinn Stefansson,Patrick Sulem,Daniel F. Gudbjartsson,Janice A. Maloney,Kwame Hoyte,Amy Gustafson,Yichin Liu,Yanmei Lu,Tushar Bhangale,Robert R. Graham,Johanna Huttenlocher,Gyda Bjornsdottir,Ole A. Andreassen,Erik G. Jönsson,Aarno Palotie,Timothy W. Behrens,Olafur T. Magnusson,Augustine Kong,Unnur Thorsteinsdottir,Unnur Thorsteinsdottir,Ryan J. Watts,Kari Stefansson,Kari Stefansson +28 more