Evidence map›Paper›PMID 40602401›Full record

ArticleCell2025

Development of clinically viable non-muscle myosin II small molecule inhibitors.

Laszlo Radnai, Erica J Young, Carlos Kikuti, Katalin Toth, Minghai Zhou, Madalyn Hafenbreidel, Rebecca F Stremel, Li Lin, Paolo Pasetto, Xiaomin Jin and 20 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Amoeboid cancer cells at a glance.Journal of cell science · 2026
    Review
  2. Review
  3. Review
  4. Review
  5. Non-muscle myosin II is a promising therapeutic target.Trends in pharmacological sciences · 2025
    Article
  6. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

30 authors.

Laszlo RadnaiDepartment of Molecular Medicine, The Scripps Research Institute and The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL 33458, USA; Department of Neuroscience, The Scripps Research Institute and The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL 33458, USA.
Erica J YoungDepartment of Molecular Medicine, The Scripps Research Institute and The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL 33458, USA; Department of Neuroscience, The Scripps Research Institute and The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL 33458, USA; Myosin Therapeutics, Jupiter, FL 33458, USA.
Carlos KikutiStructural Motility, UMR 144 CNRS/Curie Institute, PSL Research University, Paris 75248, France.
Katalin TothDepartment of Molecular Medicine, The Scripps Research Institute and The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL 33458, USA.
Minghai ZhouMyosin Therapeutics, Jupiter, FL 33458, USA.
Madalyn HafenbreidelDepartment of Molecular Medicine, The Scripps Research Institute and The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL 33458, USA; Department of Neuroscience, The Scripps Research Institute and The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL 33458, USA.
Rebecca F StremelDepartment of Molecular Medicine, The Scripps Research Institute and The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL 33458, USA; Department of Neuroscience, The Scripps Research Institute and The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL 33458, USA.
Li LinDepartment of Molecular Medicine, The Scripps Research Institute and The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL 33458, USA.
Paolo PasettoCuria, 26 Corporate Circle, Albany, NY 12203, USA.
Xiaomin JinCuria, 26 Corporate Circle, Albany, NY 12203, USA.
Aagam PatelCuria, 26 Corporate Circle, Albany, NY 12203, USA.
Michael ConlonCuria, 26 Corporate Circle, Albany, NY 12203, USA.
Sherri B BriggsDepartment of Molecular Medicine, The Scripps Research Institute and The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL 33458, USA; Department of Neuroscience, The Scripps Research Institute and The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL 33458, USA.
Leïla HeidsieckStructural Motility, UMR 144 CNRS/Curie Institute, PSL Research University, Paris 75248, France.
H Lee SweeneyDepartment of Pharmacology & Therapeutics, Myology Institute, University of Florida, Gainesville, FL 32610, USA.
James SellersLaboratory of Molecular Physiology, NHLBI, National Institutes of Health, Bethesda, MD 20892, USA.
Teresa Krieger-BurkePharmacology & Toxicology, In Vivo Facility, Michigan State University, East Lansing, MI 48824, USA.
William H MartinWHM Consulting, Lyme, CT 06371, USA.
Jay SiscoJM Sisco Pharma Consulting, Bradenton, FL 34201, USA.
Steven YoungMedicinal Chemistry, BeOne Medicines, Beigene, Zhong-Guan-Cun Life Science Park, Beijing 102206, China.
Paul PearsonPearson Pharma Partners, Thousand Oaks, CA 91362, USA.
Gavin RumbaughDepartment of Neuroscience, The Scripps Research Institute and The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL 33458, USA.
Gian Luca AraldiAvanti Biosciences, San Diego, CA 92121, USA.
Steven K DuddyToxicology, Certara, Ann Arbor, MI 48103, USA.
Michael D CameronDepartment of Molecular Medicine, The Scripps Research Institute and The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL 33458, USA.
Matthew SurmanCuria, 26 Corporate Circle, Albany, NY 12203, USA.
Anne HoudusseStructural Motility, UMR 144 CNRS/Curie Institute, PSL Research University, Paris 75248, France.
Patrick R GriffinDepartment of Molecular Medicine, The Scripps Research Institute and The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL 33458, USA.
Theodore M KameneckaDepartment of Molecular Medicine, The Scripps Research Institute and The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL 33458, USA.
Courtney A MillerDepartment of Molecular Medicine, The Scripps Research Institute and The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL 33458, USA; Department of Neuroscience, The Scripps Research Institute and The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL 33458, USA. Electronic address: cmiller@scripps.edu.

Funding

Myosin II regulation of actin dynamics and the selective vulnerability of methamphetamine- and opioid-associated memoryR01DA049544 · NIDA · UNIVERSITY OF FLORIDA · PI MILLER, COURTNEY A, RUMBAUGH, GAVIN R · 2020 to 2024
$3.6M
Development of a first-in-class nonmuscle myosin II inhibitor to prevent substance use disorder relapseR44DA055420 · NIDA · MYOSIN THERAPEUTICS INC. · PI YOUNG, ERICA J · 2021 to 2023
$3.2M
Developing nonmuscle II inhibitors for substance use relapseUH3NS096833 · NINDS · SCRIPPS FLORIDA · PI GRIFFIN, PATRICK ROBERT, KAMENECKA, THEODORE M · 2017 to 2020
$1.8M
NIDA NIH HHS R01 DA049544NIDA NIH HHS R44 DA055420NINDS NIH HHS UH3 NS096833
6 · The paper itself

Abstract

Non-muscle myosin II (NMII), a molecular motor that regulates critical processes such as cytokinesis and neuronal plasticity, has substantial therapeutic potential. However, translating this potential to in vivo use has been hampered by a lack of selective tools. The most prototypical non-selective inhibitor inactivates both NMII and cardiac muscle myosin II (CMII), a key regulator of heart function. Using rational drug design, we developed a series of NMII inhibitors that markedly improve tolerability by selectively targeting NMII over CMII, including MT-228 and clinical candidate MT-110. MT-228 and MT-110 have excellent properties, including high brain penetration and efficacy in preclinical models of methamphetamine use disorder (MUD), which has no current FDA-approved therapies. The structure of MT-228 bound to myosin II provides insight into its selectivity for NMII over CMII. The broad therapeutic windows of these NMII inhibitors provide valuable tools for the scientific community and a promising clinical candidate for the treatment of MUD.

Indexed as

Myosin Type IISmall Molecule LibrariesAnimalsHumansMethamphetamineMiceMethamphetamineMyosin Type IISmall Molecule Librariesblebbistatincancercardiac muscle myosin IIhigh-resolution protein-inhibitor structuremedicinal chemistrymethamphetaminemolecular motornon-muscle myosin IIsubstance use disordertherapeutic

Identifiers

PMID40602401
PMCPMC12233157

What OpenQuestion holds

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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.