Uncovering the Elusive Structures and Mechanisms of Prevalent Antidepressants.

Jieye Lin, Guanhong Bu, Johan Unge, Tamir Gonen

Abstract read

In one paragraph

Article in Advanced therapeutics, 2024. 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

4 authors.

Jieye LinDepartment of Biological Chemistry, University of California, Los Angeles, 615 Charles E. Young Drive South, Los Angeles, California 90095, United States.

Guanhong BuDepartment of Biological Chemistry, University of California, Los Angeles, 615 Charles E. Young Drive South, Los Angeles, California 90095, United States.

Johan UngeDepartment of Biological Chemistry, University of California, Los Angeles, 615 Charles E. Young Drive South, Los Angeles, California 90095, United States.

Tamir GonenDepartment of Biological Chemistry, University of California, Los Angeles, 615 Charles E. Young Drive South, Los Angeles, California 90095, United States.

Funding

TRD4: Design and Engineering of MicroED hardware for nanocrystallization and time resolved studiesP41GM136508 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GONEN, TAMIR · 2020 to 2024

$7.6M

Howard Hughes Medical InstituteNIGMS NIH HHS P41 GM136508

6 · The paper itself

Abstract

Most treatments to alleviate major depression work by either inhibiting human monoamine transporters, vital for the reuptake of monoamine neurotransmitters, or by inhibiting monoamine oxidases, which are vital for their degradation. The analysis of the experimental 3D structures of those antidepressants in their drug formulation state is key to precision drug design and development. In this study, we apply microcrystal electron diffraction (MicroED) to reveal the atomic 3D structures for the first time of five of the most prevalent antidepressants (reboxetine, pipofezine, ansofaxine, phenelzine, bifemelane) directly from the commercially available powder of the active ingredients. Their modes of binding are investigated by molecular docking, revealing the essential contacts and conformational changes into the biologically active state. This study underscores the combined use of MicroED and molecular docking to uncover elusive drug structures and mechanisms to aid in further drug development pipelines.

Identifiers

PMID40012744

DOI10.1002/adtp.202400117

PMCPMC11864751

What OpenQuestion holds

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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.