Evidence map›Paper›PMID 42811100›Full record

ArticleThe Journal of antibiotics2026

Amino acid mapping-guided scaffold selection and hit identification of histidine kinase inhibitors from a virtual library of over 12 million compounds.

Teruhiko Ishikawa, Yoko Eguchi, Toshihide Okajima, Masayuki Igarashi, Shino Ohira, Kyosuke Tsumura, Kazumasa Sakurai, Yoshimasa Ishizaki, Chigusa Hayashi, Shammi Akter and 8 more

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Article in The Journal of antibiotics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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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

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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

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0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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5 · Who and what money

Authors and funding

18 authors.

Teruhiko Ishikawa *Graduate School of Education, Okayama University, Okayama, Japan. teruhiko@cc.okayama-u.ac.jp.
Yoko Eguchi *Department of Science and Technology on Food Safety, Faculty of Biology-Oriented Science and Technology, Kindai University, Wakayama, Japan. eguchi@waka.kindai.ac.jp.
Toshihide Okajima *SANKEN, The University of Osaka, Osaka, Japan.ORCID http://orcid.org/0000-0003-1733-9580
Masayuki Igarashi *Institute of Microbial Chemistry (BIKAKEN), Tokyo, Japan.ORCID http://orcid.org/0000-0002-1562-6685
Shino OhiraAnalysis Technology Center, FUJIFILM Corporation, Kanagawa, Japan.
Kyosuke TsumuraAnalysis Technology Center, FUJIFILM Corporation, Kanagawa, Japan.
Kazumasa SakuraiHigh Pressure Protein Research Center, Institute of Advanced Technology, Kindai University, Wakayama, Japan.
Yoshimasa IshizakiInstitute of Microbial Chemistry (BIKAKEN), Tokyo, Japan.ORCID http://orcid.org/0000-0001-6893-0050
Chigusa HayashiInstitute of Microbial Chemistry (BIKAKEN), Tokyo, Japan.
Shammi AkterLaboratory of Microbial Technology, Division of Systems Bioengineering, Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School, Kyushu University, Fukuoka, Japan.
Jiro NakayamaLaboratory of Microbial Technology, Division of Systems Bioengineering, Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School, Kyushu University, Fukuoka, Japan.
Chie KohayakawaDepartment of Lead Exploration Units, Graduate School of Pharmaceutical Sciences, The University of Osaka, Osaka, Japan.
Akiyoshi TaniDepartment of Lead Exploration Units, Graduate School of Pharmaceutical Sciences, The University of Osaka, Osaka, Japan.ORCID http://orcid.org/0000-0001-6578-844X
Naoki SawaGraduate School of Education, Okayama University, Okayama, Japan.
Takaomi KatsumotoGraduate School of Education, Okayama University, Okayama, Japan.
Fumiya MatsumotoGraduate School of Education, Okayama University, Okayama, Japan.
Jun-Ichi HarutaDepartment of Lead Exploration Units, Graduate School of Pharmaceutical Sciences, The University of Osaka, Osaka, Japan.
Ryutaro Utsumi *SANKEN, The University of Osaka, Osaka, Japan. utsumi@sanken.osaka-u.ac.jp.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Waldiomycin is a natural product originally isolated from actinomycete extracts. It inhibits histidine kinases (HKs), which are essential components of bacterial two-component signal transduction systems, by targeting the conserved H-box region and suppressing autophosphorylation. Here, we identified novel HK inhibitors using amino acid mapping (AAM)-based virtual screening. We compared the AAM descriptor of the naphthoquinone moiety of waldiomycin, which directly interacts with the H-box region, with those of approximately 12 million commercially available compounds and identified 714 candidates with similar descriptor values. From these candidates, we selected 9-hydroxy-4H-pyrido[1,2-a]pyrimidin-4-one as a promising and structurally distinct scaffold and synthesized 15 derivatives. The inhibitory activities of these derivatives were evaluated against the HKs WalK, VicK, and EnvZ. Three 4H-pyrido[1,2-a]pyrimidin-4-one derivatives (FF-054, FF-055, and FF-060) exhibited potent inhibitory activity, with IC

Identifiers

PMID42811100

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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.