Discovery of 4-Piperazine Isoquinoline Derivatives as Potent and Brain-Permeable Tau Prion Inhibitors with CDK8 Activity.

Journal

ACS medicinal chemistry letters
ISSN: 1948-5875
Titre abrégé: ACS Med Chem Lett
Pays: United States
ID NLM: 101521073

Informations de publication

Date de publication:
13 Feb 2020
Historique:
received: 17 10 2019
accepted: 14 01 2020
entrez: 20 2 2020
pubmed: 20 2 2020
medline: 20 2 2020
Statut: epublish

Résumé

Tau prions feature in the brains of patients suffering from Alzheimer's disease and other tauopathies. For the development of therapeutics that target the replication of tau prions, a high-content, fluorescence-based cell assay was developed. Using this high-content phenotypic screen for nascent tau prion formation, a 4-piperazine isoquinoline compound (

Identifiants

DOI: 10.1021/acsmedchemlett.9b00480 PMID: 32071678 PMC: PMC7025388
pubmed: 32071678
doi: 10.1021/acsmedchemlett.9b00480
pmc: PMC7025388
doi:

Types de publication

Journal Article

Langues

eng

Pagination

127-132

Subventions

Organisme : NIA NIH HHS
ID : P01 AG002132
Pays : United States

Informations de copyright

Copyright © 2020 American Chemical Society.

Déclaration de conflit d'intérêts

The authors declare the following competing financial interest(s): The Institute for Neurodegenerative Diseases has a research collaboration with Daiichi Sankyo (Tokyo, Japan). Stanley B. Prusiner is a member of the Scientific Advisory Board of ViewPoint Therapeutics and a member of the Board of Directors of Trizell, Ltd., neither of which have contributed financial or any other support to these studies.

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Auteurs

Jean-Marc M Grandjean (JM)

Institute for Neurodegenerative Diseases (IND), UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California 94518, United States.

Alexander Y Jiu (AY)

Institute for Neurodegenerative Diseases (IND), UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California 94518, United States.

John W West (JW)

Institute for Neurodegenerative Diseases (IND), UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California 94518, United States.

Atsushi Aoyagi (A)

R&D Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.

Daniel G Droege (DG)

Institute for Neurodegenerative Diseases (IND), UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California 94518, United States.

Manuel Elepano (M)

Institute for Neurodegenerative Diseases (IND), UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California 94518, United States.

Makoto Hirasawa (M)

R&D Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.

Masakazu Hirouchi (M)

R&D Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.

Ryo Murakami (R)

R&D Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.

Joanne Lee (J)

Institute for Neurodegenerative Diseases (IND), UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California 94518, United States.

Koji Sasaki (K)

R&D Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.

Shimpei Hirano (S)

R&D Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.

Takao Ohyama (T)

R&D Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.

Benjamin C Tang (BC)

Institute for Neurodegenerative Diseases (IND), UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California 94518, United States.

Roy J Vaz (RJ)

Institute for Neurodegenerative Diseases (IND), UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California 94518, United States.

Masahiro Inoue (M)

R&D Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.

Steven H Olson (SH)

Institute for Neurodegenerative Diseases (IND), UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California 94518, United States.

Stanley B Prusiner (SB)

Institute for Neurodegenerative Diseases (IND), UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California 94518, United States.

Jay Conrad (J)

Institute for Neurodegenerative Diseases (IND), UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California 94518, United States.

Nick A Paras (NA)

Institute for Neurodegenerative Diseases (IND), UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California 94518, United States.

Classifications MeSH