Evidence map›Paper›PMID 41941629›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2026

AI-derived therapeutic development of a serotonin receptor-targeting drug for the treatment of opioid use disorder.

Valeria Lallai, Samuel Kho, A C Martin, James P Fowler, Madison L Roach, Kevin Wang, Kendyl N Laumann, Tyler G Morris, Mina Palaniappan, Malia Bautista and 14 more

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2026. 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
–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

2 citing papers in PubMed.

  1. Review
  2. AI-derived therapeutic development of a serotonin receptor-targeting drug for the treatment of opioid use disorder.Proceedings of the National Academy of Sciences of the United States of America · 2026
    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

24 authors.

Valeria LallaiDepartment of Neurobiology and Behavior, University of California, Irvine, CA 92697.ORCID 0000-0002-5674-8988
Samuel KhoGATC Health, Irvine, CA 92614.ORCID 0000-0003-2257-7292
A C MartinGATC Health, Irvine, CA 92614.
James P FowlerDepartment of Neurobiology and Behavior, University of California, Irvine, CA 92697.
Madison L RoachDepartment of Neurobiology and Behavior, University of California, Irvine, CA 92697.ORCID 0009-0001-9518-1638
Kevin WangDepartment of Neurobiology and Behavior, University of California, Irvine, CA 92697.
Kendyl N LaumannDepartment of Neurobiology and Behavior, University of California, Irvine, CA 92697.
Tyler G MorrisDepartment of Psychology, California State University, Long Beach, CA 90840.
Mina PalaniappanDepartment of Neurobiology and Behavior, University of California, Irvine, CA 92697.
Malia BautistaDepartment of Neurobiology and Behavior, University of California, Irvine, CA 92697.
Allison S MogulDepartment of Neurobiology and Behavior, University of California, Irvine, CA 92697.
Jinjutha E CheepluesakDepartment of Neurobiology and Behavior, University of California, Irvine, CA 92697.
Bijay ShresthaGATC Health, Irvine, CA 92614.ORCID 0009-0007-1341-2863
Dhanaji M LadeGATC Health, Irvine, CA 92614.ORCID 0000-0001-5191-2147
Julia E LagomarsinoDepartment of Neurobiology and Behavior, University of California, Irvine, CA 92697.
Vaishnavi NarayanGATC Health, Irvine, CA 92614.
Jayson UffensGATC Health, Irvine, CA 92614.
Waldemar LernhardtGATC Health, Irvine, CA 92614.
Saman MirzaeiGATC Health, Irvine, CA 92614.
Ian JenkinsGATC Health, Irvine, CA 92614.
Arturo R ZavalaDepartment of Psychology, California State University, Long Beach, CA 90840.ORCID 0000-0001-7884-9176
Jonathan R T LakeyGATC Health, Irvine, CA 92614.
Robert TinderGATC Health, Irvine, CA 92614.
Christie D FowlerDepartment of Neurobiology and Behavior, University of California, Irvine, CA 92697.ORCID 0000-0003-2864-2163

Funding

Dynamic epigenomic landscape of opioid abuse following early-life adversityU01DA053826 · NIDA · UNIVERSITY OF CALIFORNIA-IRVINE · PI Tallie Z. Baram, CHRISTIE D FOWLER · 2022 to 2026
$3.4M
Discovery and development of GPR3 agonists for nicotine cessationR01DA058493 · NIDA · RESEARCH TRIANGLE INSTITUTE · PI CHRISTIE D FOWLER, Elaine Arrington Gay · 2023 to 2026
$3.4M
Impact of THC on Extracellular Vesicle SignalingR01DA051831 · NIDA · UNIVERSITY OF CALIFORNIA-IRVINE · PI FOWLER, CHRISTIE D · 2020 to 2024
$2.0M
GATC Health GATCNIDA NIH HHS R01 DA051831NIDA NIH HHS R01 DA058493NIDA NIH HHS U01 DA053826Tobacco-Related Disease Research Program (TRDRP) T32IR4866Tobacco-Related Disease Research Program (TRDRP) T34IP8023
6 · The paper itself

Abstract

The opioid epidemic has led to a devastating loss of life nationwide. Of those dependent on opioids, many individuals desire to quit or reduce use, but their efforts are often unsuccessful given the powerful reinforcing properties associated with opioid drugs, including fentanyl. Here, we developed a therapeutic drug based on an AI-based platform, which was rationally designed to identify markers of dysregulation from human drug user postmortem brain tissue. Two top candidate compounds, GATC-021 and GATC-1021, were synthesized and validated with in vitro screening for target specificity. Thereafter, the drug candidates were examined for their effectiveness in modulating opioid reinforcement and intake. GATC-1021 emerged as the most efficacious compound as it significantly decreased fentanyl intake in both male and female rats, without any notable side effects. GATC-1021 was further found to modulate gene expression patterns in addiction-relevant brain regions following fentanyl-induced alterations. These findings validate GATC's AI-based platform with its polypharmacy-focused drug development approach and further support the clinical potential of GATC-1021 as a promising therapeutic for those suffering from opioid use disorder.

Indexed as

Opioid-Related DisordersReceptors, SerotoninAnalgesics, OpioidAnimalsBrainFemaleFentanylHumansMaleRatsRats, Sprague-DawleyAnalgesics, OpioidFentanylReceptors, Serotoninaddictionfentanylopioidserotonin receptortherapeutic development

Identifiers

PMID41941629
PMCPMC13079983

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.