Evidence map›Paper›PMID 35941525›Full record

ArticleArchiv der Pharmazie2022

1,4-Dihydropyridinebutyrolactone-derived ring-opened ester and amide analogs targeting BET bromodomains.

Jiewei Jiang, Pei-Liang Zhao, Logan H Sigua, Alice Chan, Ernst Schönbrunn, Jun Qi, Gunda I Georg

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

Article in Archiv der Pharmazie, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.4field-weighted citation impact, top 41% 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

2 citing papers in PubMed, 5 citations in OpenAlex.

  1. Review
  2. 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

7 authors at 4 institutions in 1 country.

Jiewei JiangDepartment of Medicinal Chemistry and Institute for Therapeutics Discovery and Development, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA.
Pei-Liang ZhaoDepartment of Medicinal Chemistry and Institute for Therapeutics Discovery and Development, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA.
Logan H SiguaDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Alice ChanDrug Discovery Department, Moffitt Cancer Center, Tampa, Florida, USA.
Ernst SchönbrunnDrug Discovery Department, Moffitt Cancer Center, Tampa, Florida, USA.
Jun QiDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Gunda I GeorgDepartment of Medicinal Chemistry and Institute for Therapeutics Discovery and Development, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA.ORCID http://orcid.org/0000-0002-8900-9460
University of Minnesota · USMoffitt Cancer Center · USDana-Farber Cancer Institute · USHarvard University · US

Funding

Understanding Behavioral Patterns in Contraceptive UseP50HD093540 · NICHD · UNIVERSITY OF MINNESOTA · PI BARBER, JENNIFER S. · 2019 to 2020
$3.9M
NICHD NIH HHS HHSN275201300017CNICHD NIH HHS HHSN275201300017INICHD NIH HHS P50 HD093540
6 · The paper itself

Abstract

Based on a previously reported 1,4-dihydropyridinebutyrolactone virtual screening hit, nine lactone ring-opened ester and seven amide analogs were prepared. The analogs were designed to provide interactions with residues at the entrance of the ZA loop of the testis-specific bromodomain (ZA) channel to enhance the affinity and selectivity for the bromodomain and extra-terminal (BET) subfamily of bromodomains. Compound testing by AlphaScreen showed that neither the affinity nor the selectivity of the ester and lactam analogs was improved for BRD4-1 and the first bromodomain of the testis-specific bromodomain (BRDT-1). The esters retained affinity comparable to the parent compound, whereas the affinity for the amide analogs was reduced 10-fold. A representative benzyl ester analog was found to retain high selectivity for BET bromodomains as shown by a BROMOscan. X-ray analysis of the allyl ester analog in complex with BRD4-1 and BRDT-1 revealed that the ester side chain is located next to the ZA loop and solvent exposed.

Indexed as

Nuclear ProteinsTranscription FactorsAmidesCell Cycle ProteinsEstersHumansLactonesMaleStructure-Activity RelationshipAmidesCell Cycle ProteinsEstersLactonesNuclear ProteinsTranscription FactorsAlphaScreenBET selectivitybromodomain and extra-terminal (BET) proteinsBROMOscanX-ray

Identifiers

PMID35941525
PMCPMC9633406
OpenAlexW4290726890

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.