BACE-1 Inhibitors: From Recent Single-Target Molecules to Multitarget Compounds for Alzheimer's Disease

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BACE-1 Inhibitors : From Recent Single-Target Molecules to Multitarget Compounds for Alzheimer's Disease. / Prati, Federica; Bottegoni, Giovanni; Bolognesi, Maria Laura; Cavalli, Andrea.

In: Journal of Medicinal Chemistry, Vol. 61, No. 3, 08.02.2018, p. 619-637.

Research output: Contribution to journalReview article

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Prati, Federica ; Bottegoni, Giovanni ; Bolognesi, Maria Laura ; Cavalli, Andrea. / BACE-1 Inhibitors : From Recent Single-Target Molecules to Multitarget Compounds for Alzheimer's Disease. In: Journal of Medicinal Chemistry. 2018 ; Vol. 61, No. 3. pp. 619-637.

Bibtex

@article{3d719d40748a498fbff5c63e82301dce,
title = "BACE-1 Inhibitors: From Recent Single-Target Molecules to Multitarget Compounds for Alzheimer's Disease",
abstract = "The amyloid hypothesis has long been the central dogma in drug discovery for Alzheimer's disease (AD), leading to many small-molecule and biological drug candidates. One major target has been the β-site amyloid-precursor-protein-cleaving enzyme 1 (BACE-1), with many big pharma companies expending great resources in the search for BACE-1 inhibitors. The lack of efficacy of verubecestat in mild-to-moderate AD raises important questions about the timing of intervention with BACE-1 inhibitors, and anti-amyloid therapies in general, in AD treatment. It also suggests new possibilities for discovering BACE-1-targeted compounds with more complex mechanisms of actions and improved efficacy. Herein, we review the major advances in BACE-1 drug discovery, from single-target small molecule inhibitors to multitarget compounds. We discuss these compounds as innovative tools for better understanding the complexity of AD and for identifying efficacious drug candidates to treat this devastating disease.",
author = "Federica Prati and Giovanni Bottegoni and Bolognesi, {Maria Laura} and Andrea Cavalli",
year = "2018",
month = feb
day = "8",
doi = "10.1021/acs.jmedchem.7b00393",
language = "English",
volume = "61",
pages = "619--637",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "3",

}

RIS

TY - JOUR

T1 - BACE-1 Inhibitors

T2 - From Recent Single-Target Molecules to Multitarget Compounds for Alzheimer's Disease

AU - Prati, Federica

AU - Bottegoni, Giovanni

AU - Bolognesi, Maria Laura

AU - Cavalli, Andrea

PY - 2018/2/8

Y1 - 2018/2/8

N2 - The amyloid hypothesis has long been the central dogma in drug discovery for Alzheimer's disease (AD), leading to many small-molecule and biological drug candidates. One major target has been the β-site amyloid-precursor-protein-cleaving enzyme 1 (BACE-1), with many big pharma companies expending great resources in the search for BACE-1 inhibitors. The lack of efficacy of verubecestat in mild-to-moderate AD raises important questions about the timing of intervention with BACE-1 inhibitors, and anti-amyloid therapies in general, in AD treatment. It also suggests new possibilities for discovering BACE-1-targeted compounds with more complex mechanisms of actions and improved efficacy. Herein, we review the major advances in BACE-1 drug discovery, from single-target small molecule inhibitors to multitarget compounds. We discuss these compounds as innovative tools for better understanding the complexity of AD and for identifying efficacious drug candidates to treat this devastating disease.

AB - The amyloid hypothesis has long been the central dogma in drug discovery for Alzheimer's disease (AD), leading to many small-molecule and biological drug candidates. One major target has been the β-site amyloid-precursor-protein-cleaving enzyme 1 (BACE-1), with many big pharma companies expending great resources in the search for BACE-1 inhibitors. The lack of efficacy of verubecestat in mild-to-moderate AD raises important questions about the timing of intervention with BACE-1 inhibitors, and anti-amyloid therapies in general, in AD treatment. It also suggests new possibilities for discovering BACE-1-targeted compounds with more complex mechanisms of actions and improved efficacy. Herein, we review the major advances in BACE-1 drug discovery, from single-target small molecule inhibitors to multitarget compounds. We discuss these compounds as innovative tools for better understanding the complexity of AD and for identifying efficacious drug candidates to treat this devastating disease.

UR - http://www.scopus.com/inward/record.url?scp=85041804152&partnerID=8YFLogxK

U2 - 10.1021/acs.jmedchem.7b00393

DO - 10.1021/acs.jmedchem.7b00393

M3 - Review article

AN - SCOPUS:85041804152

VL - 61

SP - 619

EP - 637

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 3

ER -