Evidence map›Paper›PMID 41557480›Full record

ArticleJournal of medicinal chemistry2026

Diastereomeric Branched-Ester dBET1 Analogs Exhibit Conformation-Dependent Differences in Passive Membrane Permeability.

Mazin A S Abdelwahid, Eisuke Hayakawa, Keigo Hirai, Mayumi Ishii, Kayoko Kanamitsu, Saori Yasuda, Fumiaki Ohtake, Shinichi Sato, Shusuke Tomoshige, Minoru Ishikawa

Abstract read
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In one paragraph

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

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Mazin A S AbdelwahidGraduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, Japan.
Eisuke HayakawaGraduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, Japan.
Keigo HiraiGraduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, Japan.
Mayumi IshiiGraduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Kayoko KanamitsuGraduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Saori YasudaGraduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, Japan.
Fumiaki OhtakeSchool of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-Ku, Tokyo 142-8501, Japan.
Shinichi SatoGraduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, Japan.
Shusuke TomoshigeGraduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, Japan.ORCID 0000-0002-4948-5809
Minoru IshikawaGraduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, Japan.ORCID 0000-0002-3937-2261

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Proteolysis-targeting chimeras (PROTACs) represent a promising therapeutic modality, but their clinical translation is often hindered by poor pharmacokinetic properties associated with their location in the "beyond Rule of 5" chemical space. Using the BRD4 degrader dBET1 as a model, this study explored a dual approach to improve the cellular permeability of PROTACs by combining amide-to-ester substitution with the strategic linker methylation to induce stereochemistry-driven conformational modulation. Substitution with ester enhanced both permeability and degradation potency, while methylation afforded two diastereomers with different permeability profiles. Steered molecular dynamics and enhanced conformational sampling in polar and nonpolar environments revealed distinct chameleonic behaviors, with the more permeable diastereomer

Indexed as

Cell Membrane PermeabilityEstersBromodomain Containing ProteinsCell Cycle ProteinsHumansMolecular ConformationMolecular Dynamics SimulationProteolysis Targeting ChimeraStereoisomerismTranscription FactorsBRD4 protein, humanBromodomain Containing ProteinsCell Cycle ProteinsEstersProteolysis Targeting ChimeraTranscription Factors

Identifiers

PMID41557480
PMCPMC12910643

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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.