Evidence map›Paper›PMID 32016207›Full record

ArticleChemical communications (Cambridge, England)2020

Substrate interaction inhibits γ-secretase production of amyloid-β peptides.

Jing Zhao, Yuanyuan Xiao, Xinyue Liu, Soohyun Kim, Xianzhong Wu, Marilia Barros, Ran Zhuang, Xuben Hou, Yingkai Zhang, Nikolaos K Robakis and 4 more

Open access · hybridAbstract read
In one paragraph

Article in Chemical communications (Cambridge, England), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.5field-weighted citation impact, top 37% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. Covalent fragment inhibits intramembrane proteolysis.Frontiers in molecular biosciences · 2022
    Article
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 6 institutions in 4 countries.

Jing ZhaoCenter for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA. wangc5@rpi.edu.ORCID http://orcid.org/0000-0002-7031-3024
Yuanyuan XiaoCenter for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA. wangc5@rpi.edu.
Xinyue LiuCenter for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA. wangc5@rpi.edu.
Soohyun KimCenter for Molecular Biology and Genetics of Neurodegeneration, Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Xianzhong WuChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Marilia BarrosChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Ran ZhuangCenter for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA. wangc5@rpi.edu.
Xuben HouDepartment of Medicinal Chemistry and Key Laboratory of Chemical Biology of Natural Products (MOE), School of Pharmacy, Shandong University, Jinan, Shandong 250012, China.
Yingkai ZhangDepartment of Chemistry, New York University, New York, NY 10003, USA.
Nikolaos K RobakisCenter for Molecular Biology and Genetics of Neurodegeneration, Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Yue-Ming LiChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Jonathan S DordickCenter for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA. wangc5@rpi.edu and Department of Biological Sciences, Rensselaer Polytechnic Institute, Troy, NY 12180, USA and Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
Iban Ubarretxena-BelandiaDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA and Instituto Biofisika (UPV/EHU, CSIC), University of the Basque Country, E-48940, Leioa, Spain and Ikerbasque, Basque Foundation for Science, 48013, Bilbao, Spain.
Chunyu WangCenter for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA. wangc5@rpi.edu and Department of Biological Sciences, Rensselaer Polytechnic Institute, Troy, NY 12180, USA and Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.ORCID http://orcid.org/0000-0001-5165-7959
Rensselaer Polytechnic Institute · USMemorial Sloan Kettering Cancer Center · USIcahn School of Medicine at Mount Sinai · USIkerbasque · ESNew York University · USShandong University · CN

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
Regulation of ephrinB2-dependent angiogenesis by PS1 in normal and ADR01NS047229 · NINDS · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI GEORGAKOPOULOS, ANASTASIOS, ROBAKIS, NIKOLAOS K · 2004 to 2025
$8.3M
STRUCTURE &EXPRESSION OF THE B-PROTEIN-PRECURSOR GENER01AG008200 · NIA · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI ROBAKIS, NIKOLAOS K · 1988 to 2017
$5.6M
Computational modulator design and machine learning to target protein-protein interactionsR35GM127040 · NIGMS · NEW YORK UNIVERSITY · PI Yingkai Zhang · 2018 to 2026
$4.6M
Predoctoral Training Program for Alzheimer’s Disease at the Interface of Data Science, Engineering and BiologyT32AG078123 · NIA · RENSSELAER POLYTECHNIC INSTITUTE · PI Chunyu Wang · 2023 to 2026
$974k
Structural Basis of Substrate Docking in Intramembrane ProteolysisR21NS109926 · NINDS · RENSSELAER POLYTECHNIC INSTITUTE · PI WANG, CHUNYU · 2019 to 2019
$469k
Single molecule kinetic studies of gamma-secretase/substrate interaction and the effects of AD-causing mutationsR21AG067436 · NIA · RENSSELAER POLYTECHNIC INSTITUTE · PI FORTH, SCOTT THOMAS, WANG, CHUNYU · 2021 to 2022
$426k
NCI NIH HHS P30 CA008748NIA NIH HHS R01 AG008200NIA NIH HHS R21 AG067436NIA NIH HHS T32 AG078123NIGMS NIH HHS R35 GM127040NINDS NIH HHS R01 NS047229NINDS NIH HHS R21 NS109926
6 · The paper itself

Abstract

Combining NMR, mass spectrometry, AlphaLISA and cell assays, we discovered a compound C1 that binds C-terminal juxtamembrane lysines at the transmembrane domain of the amyloid precursor protein (APPTM) and inhibits γ-secretase production of amyloid-β with μM IC50. Our work suggests that targeting APPTM is a novel and viable strategy in AD drug discovery.

Indexed as

Amyloid beta-PeptidesAmyloid Precursor Protein SecretasesHEK293 CellsHumansMass SpectrometryNuclear Magnetic Resonance, BiomolecularSubstrate SpecificityAmyloid beta-PeptidesAmyloid Precursor Protein Secretases

Identifiers

PMID32016207
PMCPMC8219260
OpenAlexW3003902266

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.