Evidence map›Paper›PMID 37841588›Full record

ArticleiScience2023

Development of novel cytoprotective small compounds inhibiting mitochondria-dependent cell death.

Mieko Matsuyama, Joseph T Ortega, Yuri Fedorov, Jonah Scott-McKean, Jeannie Muller-Greven, Matthias Buck, Drew Adams, Beata Jastrzebska, William Greenlee, Shigemi Matsuyama

Open access · goldAbstract read
In one paragraph

Article in iScience, 2023. 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
0.8field-weighted citation impact, top 27% 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, 5 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
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

10 authors at 2 institutions in 1 country.

Mieko MatsuyamaDepartment of Ophthalmology and Visual Science, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Joseph T OrtegaDepartment of Pharmacology and Cleveland Center for Membrane and Structural Biology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Yuri FedorovDepartment of Genetics and Genome Science, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Jonah Scott-McKeanDepartment of Ophthalmology and Visual Science, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Jeannie Muller-GrevenDepartment of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Matthias BuckDepartment of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Drew AdamsDepartment of Genetics and Genome Science, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Beata JastrzebskaDepartment of Pharmacology and Cleveland Center for Membrane and Structural Biology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
William GreenleeHarrington Discovery Institute, Cleveland, OH 44106, USA.
Shigemi MatsuyamaDepartment of Ophthalmology and Visual Science, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Case Western Reserve University · USCase Comprehensive Cancer Center

Funding

TUMOR METABOLISM PROGRAMP30CA043703 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI MARK R CHANCE · 1987 to 2026
$142.3M
TISSUE CULTURE AND HYBRIDOMA MODULEP30EY011373 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI Irina A Pikuleva · 1997 to 2026
$17.7M
Structure and function of plexin - co-receptor interactionsR01EY029169 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI BUCK, MATTHIAS · 2018 to 2021
$2.1M
Novel neuroprotective activities of flavonoids against retinal degenerative diseasesR01EY032874 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI JASTRZEBSKA, BEATA · 2022 to 2025
$1.9M
Bax Activation Mechanism in the CytosolR01AG031903 · NIA · CASE WESTERN RESERVE UNIVERSITY · PI MATSUYAMA, SHIGEMI · 2008 to 2012
$1.4M
NCI NIH HHS P30 CA043703NEI NIH HHS P30 EY011373NEI NIH HHS R01 EY029169NEI NIH HHS R01 EY032874NIA NIH HHS R01 AG031903
6 · The paper itself

Abstract

We identified cytoprotective small molecules (CSMs) by a cell-based high-throughput screening of Bax inhibitors. Through a medicinal chemistry program, M109S was developed, which is orally bioactive and penetrates the blood-brain/retina barriers. M109S protected retinal cells in ocular disease mouse models. M109S directly interacted with Bax and inhibited the conformational change and mitochondrial translocation of Bax. M109S inhibited ABT-737-induced apoptosis both in Bax-only and Bak-only mouse embryonic fibroblasts. M109S also inhibited apoptosis induced by staurosporine, etoposide, and obatoclax. M109S decreased maximal mitochondrial oxygen consumption rate and reactive oxygen species production, whereas it increased glycolysis. These effects on cellular metabolism may contribute to the cytoprotective activity of M109S. M109S is a novel small molecule protecting cells from mitochondria-dependent apoptosis both

Indexed as

Cell biologyCellular physiologyChemistry

Identifiers

PMID37841588
PMCPMC10568349
OpenAlexW4386813163

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.