Evidence map›Paper›PMID 36040095›Full record

ArticleChemMedChem2022

Discovery of Benzo[d]imidazole-6-sulfonamides as Bromodomain and Extra-Terminal Domain (BET) Inhibitors with Selectivity for the First Bromodomain.

Alessandra Cipriano, Ciro Milite, Alessandra Feoli, Monica Viviano, Giacomo Pepe, Pietro Campiglia, Giuliana Sarno, Sarah Picaud, Satomi Imaide, Nikolai Makukhin and 4 more

Abstract read
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In one paragraph

Article in ChemMedChem, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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

5 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. 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

14 authors.

Alessandra CiprianoDepartment of Pharmacy, University of Salerno, via Giovanni Paolo II 132, 84084, Fisciano (SA), Italy.ORCID 0000-0002-9062-5914
Ciro MiliteDepartment of Pharmacy, University of Salerno, via Giovanni Paolo II 132, 84084, Fisciano (SA), Italy.ORCID 0000-0003-1000-1376
Alessandra FeoliDepartment of Pharmacy, University of Salerno, via Giovanni Paolo II 132, 84084, Fisciano (SA), Italy.ORCID 0000-0002-8960-7858
Monica VivianoDepartment of Pharmacy, University of Salerno, via Giovanni Paolo II 132, 84084, Fisciano (SA), Italy.ORCID 0000-0003-1118-790X
Giacomo PepeDepartment of Pharmacy, University of Salerno, via Giovanni Paolo II 132, 84084, Fisciano (SA), Italy.ORCID 0000-0002-7561-2023
Pietro CampigliaDepartment of Pharmacy, University of Salerno, via Giovanni Paolo II 132, 84084, Fisciano (SA), Italy.ORCID 0000-0002-1069-2181
Giuliana SarnoDepartment of Pharmacy, University of Salerno, via Giovanni Paolo II 132, 84084, Fisciano (SA), Italy.ORCID 0000-0002-3136-0469
Sarah PicaudNuffield Department of Medicine, Oxford University, OX3 7DQ, Oxford, UK.ORCID 0000-0002-3803-4455
Satomi ImaideDivision of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH, Scotland, UK.ORCID 0000-0003-4372-4693
Nikolai MakukhinDivision of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH, Scotland, UK.ORCID 0000-0003-2465-0748
Panagis FilippakopoulosNuffield Department of Medicine, Oxford University, OX3 7DQ, Oxford, UK.ORCID 0000-0002-1515-1317
Alessio CiulliDivision of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH, Scotland, UK.ORCID 0000-0002-8654-1670
Sabrina CastellanoDepartment of Pharmacy, University of Salerno, via Giovanni Paolo II 132, 84084, Fisciano (SA), Italy.ORCID 0000-0002-7449-3704
Gianluca SbardellaDepartment of Pharmacy, University of Salerno, via Giovanni Paolo II 132, 84084, Fisciano (SA), Italy.ORCID 0000-0003-0748-1145

Funding

Biotechnology and Biological Sciences Research Council BB/J001201/2Medical Research Council MR/N010051/1Wellcome TrustWellcome Trust 094090/Z/10/ZWellcome Trust 095751/Z/11/ZWellcome Trust 100476/Z/12/Z
6 · The paper itself

Abstract

The bromodomain and extra-terminal (BET) family of proteins includes BRD2, BRD3, BRD4, and the testis-specific protein, BRDT, each containing two N-terminal tandem bromodomain (BRD) modules. Potent and selective inhibitors targeting the two bromodomains are required to elucidate their biological role(s), with potential clinical applications. In this study, we designed and synthesized a series of benzimidazole-6-sulfonamides starting from the azobenzene compounds MS436 (7 a) and MS611 (7 b) that exhibited preference for the first (BD1) over the second (BD2) BRD of BET family members. The most-promising compound (9 a) showed good binding potency and improved metabolic stability and selectivity towards BD1 with respect to the parent compounds.

Indexed as

Nuclear ProteinsSulfonamidesBenzimidazolesBenzo(a)pyreneCell Cycle ProteinsHumansImidazolesMaleTranscription FactorsBenzimidazolesBenzo(a)pyreneCell Cycle ProteinsImidazolesNuclear ProteinsSulfonamidesTranscription FactorsBenzimidazole-6-sulfonamideBioisosteresBromodomainSelectivityStructure-activity relationships

Identifiers

PMID36040095
PMCPMC9826262

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Registered trials

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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.