Evidence map›Paper›PMID 33472023›Full record

ArticleCell chemical biology2021

Designed PKC-targeting bryostatin analogs modulate innate immunity and neuroinflammation.

Efrat Abramson, Clayton Hardman, Akira J Shimizu, Soonmyung Hwang, Lynda D Hester, Solomon H Snyder, Paul A Wender, Paul M Kim, Michael D Kornberg

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell chemical biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.2field-weighted citation impact, top 22% 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

10 citing papers in PubMed, 19 citations in OpenAlex.

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  9. β-Lactams from the Ocean.Marine drugs · 2023
    Review
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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

9 authors at 2 institutions in 1 country.

Efrat AbramsonDepartment of Neurology, Johns Hopkins University, Baltimore, MD 21287, USA.
Clayton HardmanDepartments of Chemistry and of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA.
Akira J ShimizuDepartments of Chemistry and of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA.
Soonmyung HwangDepartment of Neurology, Johns Hopkins University, Baltimore, MD 21287, USA.
Lynda D HesterDepartment of Neuroscience, Johns Hopkins University, Baltimore, MD 21205, USA.
Solomon H SnyderDepartment of Neuroscience, Johns Hopkins University, Baltimore, MD 21205, USA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD 21287, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University, Baltimore, MD 21205, USA.
Paul A WenderDepartments of Chemistry and of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA.
Paul M KimDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD 21287, USA. Electronic address: pmkim@jhmi.edu.
Michael D KornbergDepartment of Neurology, Johns Hopkins University, Baltimore, MD 21287, USA. Electronic address: michael.kornberg@jhmi.edu.
Johns Hopkins University · USStanford University · US

Funding

Thorase Regulation of the Actions of CocaineP50DA044123 · NIDA · JOHNS HOPKINS UNIVERSITY · PI DAWSON, VALINA L., JANAK, PATRICIA H. · 2018 to 2022
$9.0M
SYNTHETIC STUDIES RELATED TO CANCER RESEARCH/TREATMENTR01CA031845 · NCI · STANFORD UNIVERSITY · PI PAUL Anthony WENDER · 1985 to 2026
$6.9M
Synthetic Studies Related to Cancer Research/TreatmentR37CA031845 · NCI · STANFORD UNIVERSITY · PI WENDER, PAUL ANTHONY · 2006 to 2015
$4.5M
NCI NIH HHS R01 CA031845NCI NIH HHS R37 CA031845NIDA NIH HHS P50 DA044123
6 · The paper itself

Abstract

Neuroinflammation characterizes multiple neurologic diseases, including primary inflammatory conditions such as multiple sclerosis and classical neurodegenerative diseases. Aberrant activation of the innate immune system contributes to disease progression, but drugs modulating innate immunity, particularly within the central nervous system (CNS), are lacking. The CNS-penetrant natural product bryostatin-1 attenuates neuroinflammation by targeting innate myeloid cells. Supplies of natural bryostatin-1 are limited, but a recent scalable good manufacturing practice (GMP) synthesis has enabled access to it and its analogs (bryologs), the latter providing a path to more efficacious, better tolerated, and more accessible agents. Here, we show that multiple synthetically accessible bryologs replicate the anti-inflammatory effects of bryostatin-1 on innate immune cells in vitro, and a lead bryolog attenuates neuroinflammation in vivo, actions mechanistically dependent on protein kinase C (PKC) binding. Our findings identify bryologs as promising drug candidates for targeting innate immunity in neuroinflammation and create a platform for evaluation of synthetic PKC modulators in neuroinflammatory diseases.

Indexed as

Drug DesignAnimalsBryostatinsFemaleImmunity, InnateInflammationMiceMice, Inbred C57BLMolecular ConformationPregnancyProtein Kinase C-deltaProtein Kinase InhibitorsStereoisomerismbryostatin 1BryostatinsPrkcd protein, mouseProtein Kinase C-deltaProtein Kinase InhibitorsbryologbryostatinEAEinnate immunitymicrogliamultiple sclerosisneuroinflammationPKCprostratin

Identifiers

PMID33472023
PMCPMC8052272
OpenAlexW3125561409

What OpenQuestion holds

Textmetadata
LicenceTDM
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 OpenQuestion graph.