Evidence map›Paper›PMID 35932566›Full record

ArticleEuropean journal of medicinal chemistry2022

Identification of 2-hydroxybenzoic acid derivatives as selective SIRT5 inhibitors.

Yanghan Liu, Bikash Debnath, Surinder Kumar, David B Lombard, Nouri Neamati

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

Article in European journal of medicinal chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.0field-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

4 citing papers in PubMed, 9 citations in OpenAlex.

  1. Review
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  4. 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

5 authors at 1 institution in 2 countries.

Yanghan LiuState Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, 541004, PR China; Department of Medicinal Chemistry, College of Pharmacy and Rogel Cancer Center, University of Michigan, Ann Arbor, MI, 48109, United States.
Bikash DebnathDepartment of Medicinal Chemistry, College of Pharmacy and Rogel Cancer Center, University of Michigan, Ann Arbor, MI, 48109, United States.
Surinder KumarDepartment of Pathology and Rogel Cancer Center, University of Michigan, Ann Arbor, MI, 48109, United States; Department of Pathology & Laboratory Medicine, Sylvester Comprehensive Cancer Center, Miami, FL, 33136, United States.
David B LombardDepartment of Pathology and Rogel Cancer Center, University of Michigan, Ann Arbor, MI, 48109, United States; Department of Pathology & Laboratory Medicine, Sylvester Comprehensive Cancer Center, Miami, FL, 33136, United States. Electronic address: dbl68@miami.edu.
Nouri NeamatiDepartment of Medicinal Chemistry, College of Pharmacy and Rogel Cancer Center, University of Michigan, Ann Arbor, MI, 48109, United States. Electronic address: neamati@umich.edu.
University of Michigan · US

Funding

Regulation of one carbon metabolism and epigenetics by SIRT5R01GM101171 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LOMBARD, DAVID BENNER · 2012 to 2021
$2.6M
SIRT5 inhibitors and degraders as novel treatments for Ewing sarcomaR01CA253986 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI David Benner Lombard, NOURI NEAMATI · 2022 to 2026
$2.1M
NCI NIH HHS R01 CA253986NIGMS NIH HHS R01 GM101171
6 · The paper itself

Abstract

The sirtuin deacetylase SIRT5 plays important roles in regulating multiple metabolic pathways, and potentially represents an attractive target for the treatment of several human diseases, especially cancer. In this study, we report the identification of the hit compound 11 bearing a 2-hydroxybenzoic acid functional group as a novel SIRT5-selective inhibitor via our medium-throughput thermal shift screening assay. Hit 11 stabilizes SIRT5 in a dose-dependent manner and shows moderate inhibitory activity against SIRT5 and high subtype selectivity over SIRT1, 2, and 3 in a trypsin coupled enzyme-based assay. The carboxylic acid and the adjacent hydroxyl group of 11 are essential for maintaining activity. To further improve the potency of compound 11, a lead optimization was carried out, resulting in compound 43 with a 10-fold improved potency. Overall, compound 11 represents a promising new chemical scaffold for further investigation to develop SIRT5-selective inhibitors.

Indexed as

NeoplasmsSirtuinsEnzyme AssaysHumansSalicylic AcidSirtuin 1Salicylic AcidSIRT5 protein, humanSirtuin 1Sirtuins2-Hydroxybenzoic acidMolecular dockingProtein-ligand interactions fingerprintingSIRT5 inhibitorsStructure-activity relationship

Identifiers

PMID35932566
PMCPMC10206524
OpenAlexW4286436529

What OpenQuestion holds

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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.