Evidence map›Paper›PMID 36549866›Full record

ReviewPharmacological reviews2023

Molecular Tweezers: Supramolecular Hosts with Broad-Spectrum Biological Applications.

Hedieh Shahpasand-Kroner, Ibrar Siddique, Ravinder Malik, Gabriel R Linares, Magdalena I Ivanova, Justin Ichida, Tatjana Weil, Jan Münch, Elsa Sanchez-Garcia, Frank-Gerrit Klärner and 2 more

Open access · greenAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Pharmacological reviews, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.1field-weighted citation impact, top 11% of its field
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

11 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. Naphthalimide-Buckybowl Tweezer for Selective Recognition of Fullerene CChemistry (Weinheim an der Bergstrasse, Germany) · 2025
    Article
  7. Review
  8. Article
  9. Article
  10. Molecular Machines For The Control Of Transmembrane Transport.Journal of the American Chemical Society · 2023
    Review
  11. Biospektrum : Zeitschrift der Gesellschaft fur Biologishe Chemie (GBCH) und der Vereinigung fur Allgemeine und Angewandte Mikrobiologie (VAAM) · 2023
    Review
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

12 authors at 4 institutions in 2 countries.

Hedieh Shahpasand-KronerDepartment of Neurology, David Geffen School of Medicine (H.S.-K., I.S., R.M., G.B.), Brain Research Institute (G.B.), and Molecular Biology Institute (G.B.), University of California, Los Angeles, California; Department of Stem Cell Biology & Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California (G.R.L., J.I.); Department of Neurology, University of Michigan, Ann Arbor, Michigan (M.I.I.); Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany (T.W., J.M.); and Department of Computational Biochemistry (E.S.-G.) and Faculty of Chemistry (F-G.K., T.S.), University of Duisburg-Essen, Essen, Germany.
Ibrar SiddiqueDepartment of Neurology, David Geffen School of Medicine (H.S.-K., I.S., R.M., G.B.), Brain Research Institute (G.B.), and Molecular Biology Institute (G.B.), University of California, Los Angeles, California; Department of Stem Cell Biology & Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California (G.R.L., J.I.); Department of Neurology, University of Michigan, Ann Arbor, Michigan (M.I.I.); Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany (T.W., J.M.); and Department of Computational Biochemistry (E.S.-G.) and Faculty of Chemistry (F-G.K., T.S.), University of Duisburg-Essen, Essen, Germany.
Ravinder MalikDepartment of Neurology, David Geffen School of Medicine (H.S.-K., I.S., R.M., G.B.), Brain Research Institute (G.B.), and Molecular Biology Institute (G.B.), University of California, Los Angeles, California; Department of Stem Cell Biology & Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California (G.R.L., J.I.); Department of Neurology, University of Michigan, Ann Arbor, Michigan (M.I.I.); Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany (T.W., J.M.); and Department of Computational Biochemistry (E.S.-G.) and Faculty of Chemistry (F-G.K., T.S.), University of Duisburg-Essen, Essen, Germany.
Gabriel R LinaresDepartment of Neurology, David Geffen School of Medicine (H.S.-K., I.S., R.M., G.B.), Brain Research Institute (G.B.), and Molecular Biology Institute (G.B.), University of California, Los Angeles, California; Department of Stem Cell Biology & Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California (G.R.L., J.I.); Department of Neurology, University of Michigan, Ann Arbor, Michigan (M.I.I.); Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany (T.W., J.M.); and Department of Computational Biochemistry (E.S.-G.) and Faculty of Chemistry (F-G.K., T.S.), University of Duisburg-Essen, Essen, Germany.
Magdalena I IvanovaDepartment of Neurology, David Geffen School of Medicine (H.S.-K., I.S., R.M., G.B.), Brain Research Institute (G.B.), and Molecular Biology Institute (G.B.), University of California, Los Angeles, California; Department of Stem Cell Biology & Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California (G.R.L., J.I.); Department of Neurology, University of Michigan, Ann Arbor, Michigan (M.I.I.); Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany (T.W., J.M.); and Department of Computational Biochemistry (E.S.-G.) and Faculty of Chemistry (F-G.K., T.S.), University of Duisburg-Essen, Essen, Germany.
Justin IchidaDepartment of Neurology, David Geffen School of Medicine (H.S.-K., I.S., R.M., G.B.), Brain Research Institute (G.B.), and Molecular Biology Institute (G.B.), University of California, Los Angeles, California; Department of Stem Cell Biology & Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California (G.R.L., J.I.); Department of Neurology, University of Michigan, Ann Arbor, Michigan (M.I.I.); Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany (T.W., J.M.); and Department of Computational Biochemistry (E.S.-G.) and Faculty of Chemistry (F-G.K., T.S.), University of Duisburg-Essen, Essen, Germany.
Tatjana WeilDepartment of Neurology, David Geffen School of Medicine (H.S.-K., I.S., R.M., G.B.), Brain Research Institute (G.B.), and Molecular Biology Institute (G.B.), University of California, Los Angeles, California; Department of Stem Cell Biology & Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California (G.R.L., J.I.); Department of Neurology, University of Michigan, Ann Arbor, Michigan (M.I.I.); Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany (T.W., J.M.); and Department of Computational Biochemistry (E.S.-G.) and Faculty of Chemistry (F-G.K., T.S.), University of Duisburg-Essen, Essen, Germany.
Jan MünchDepartment of Neurology, David Geffen School of Medicine (H.S.-K., I.S., R.M., G.B.), Brain Research Institute (G.B.), and Molecular Biology Institute (G.B.), University of California, Los Angeles, California; Department of Stem Cell Biology & Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California (G.R.L., J.I.); Department of Neurology, University of Michigan, Ann Arbor, Michigan (M.I.I.); Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany (T.W., J.M.); and Department of Computational Biochemistry (E.S.-G.) and Faculty of Chemistry (F-G.K., T.S.), University of Duisburg-Essen, Essen, Germany.
Elsa Sanchez-GarciaDepartment of Neurology, David Geffen School of Medicine (H.S.-K., I.S., R.M., G.B.), Brain Research Institute (G.B.), and Molecular Biology Institute (G.B.), University of California, Los Angeles, California; Department of Stem Cell Biology & Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California (G.R.L., J.I.); Department of Neurology, University of Michigan, Ann Arbor, Michigan (M.I.I.); Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany (T.W., J.M.); and Department of Computational Biochemistry (E.S.-G.) and Faculty of Chemistry (F-G.K., T.S.), University of Duisburg-Essen, Essen, Germany.
Frank-Gerrit KlärnerDepartment of Neurology, David Geffen School of Medicine (H.S.-K., I.S., R.M., G.B.), Brain Research Institute (G.B.), and Molecular Biology Institute (G.B.), University of California, Los Angeles, California; Department of Stem Cell Biology & Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California (G.R.L., J.I.); Department of Neurology, University of Michigan, Ann Arbor, Michigan (M.I.I.); Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany (T.W., J.M.); and Department of Computational Biochemistry (E.S.-G.) and Faculty of Chemistry (F-G.K., T.S.), University of Duisburg-Essen, Essen, Germany.
Thomas SchraderDepartment of Neurology, David Geffen School of Medicine (H.S.-K., I.S., R.M., G.B.), Brain Research Institute (G.B.), and Molecular Biology Institute (G.B.), University of California, Los Angeles, California; Department of Stem Cell Biology & Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California (G.R.L., J.I.); Department of Neurology, University of Michigan, Ann Arbor, Michigan (M.I.I.); Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany (T.W., J.M.); and Department of Computational Biochemistry (E.S.-G.) and Faculty of Chemistry (F-G.K., T.S.), University of Duisburg-Essen, Essen, Germany.
Gal BitanDepartment of Neurology, David Geffen School of Medicine (H.S.-K., I.S., R.M., G.B.), Brain Research Institute (G.B.), and Molecular Biology Institute (G.B.), University of California, Los Angeles, California; Department of Stem Cell Biology & Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California (G.R.L., J.I.); Department of Neurology, University of Michigan, Ann Arbor, Michigan (M.I.I.); Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany (T.W., J.M.); and Department of Computational Biochemistry (E.S.-G.) and Faculty of Chemistry (F-G.K., T.S.), University of Duisburg-Essen, Essen, Germany gbitan@mednet.ucla.edu.
University of Duisburg-Essen · DEUniversität Ulm · DEUniversity of California, Los Angeles · USUniversity of Michigan–Ann Arbor · US

Funding

UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
UCLA ALZHEIMERS DISEASE RESEARCH CENTERP50AG016570 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI APOSTOLOVA, LIANA G · 1999 to 2014
$25.9M
UCLA CENTER FOR THE STUDY OF PARKINSON'S DISEASEP50NS038367 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHESSELET, MARIE-FRANCOISE S · 1999 to 2011
$15.3M
Project 4: Pesticides and Genes In PD: Studies In HumansP01ES016732 · NIEHS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHESSELET, MARIE-FRANCOISE S · 2008 to 2012
$6.7M
Investigation of the Effect of Structural Modifications of Tau on Assembly State and SeedingRF1AG054000 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BITAN, GAL · 2017 to 2021
$2.1M
Misfolded protein-clearance enhancers for Alzheimer's therapyR01AG050721 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BITAN, GAL · 2015 to 2019
$2.0M
NCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1 TR001881NIA NIH HHS P50 AG016570NIA NIH HHS R01 AG050721NIA NIH HHS RF1 AG054000NIEHS NIH HHS P01 ES016732NINDS NIH HHS P50 NS038367
6 · The paper itself

Abstract

Lysine-selective molecular tweezers (MTs) are supramolecular host molecules displaying a remarkably broad spectrum of biologic activities. MTs act as inhibitors of the self-assembly and toxicity of amyloidogenic proteins using a unique mechanism. They destroy viral membranes and inhibit infection by enveloped viruses, such as HIV-1 and SARS-CoV-2, by mechanisms unrelated to their action on protein self-assembly. They also disrupt biofilm of Gram-positive bacteria. The efficacy and safety of MTs have been demonstrated in vitro, in cell culture, and in vivo, suggesting that these versatile compounds are attractive therapeutic candidates for various diseases, infections, and injuries. A lead compound called CLR01 has been shown to inhibit the aggregation of various amyloidogenic proteins, facilitate their clearance in vivo, prevent infection by multiple viruses, display potent anti-biofilm activity, and have a high safety margin in animal models. The inhibitory effect of CLR01 against amyloidogenic proteins is highly specific to abnormal self-assembly of amyloidogenic proteins with no disruption of normal mammalian biologic processes at the doses needed for inhibition. Therapeutic effects of CLR01 have been demonstrated in animal models of proteinopathies, lysosomal-storage diseases, and spinal-cord injury. Here we review the activity and mechanisms of action of these intriguing compounds and discuss future research directions. SIGNIFICANCE STATEMENT: Molecular tweezers are supramolecular host molecules with broad biological applications, including inhibition of abnormal protein aggregation, facilitation of lysosomal clearance of toxic aggregates, disruption of viral membranes, and interference of biofilm formation by Gram-positive bacteria. This review discusses the molecular and cellular mechanisms of action of the molecular tweezers, including the discovery of distinct mechanisms acting in vitro and in vivo, and the application of these compounds in multiple preclinical disease models.

Indexed as

Biological ProductsCOVID-19Amyloidogenic ProteinsAnimalsMammalsOrganophosphatesSARS-CoV-2Amyloidogenic ProteinsBiological ProductsOrganophosphates

Identifiers

PMID36549866
PMCPMC9976797
OpenAlexW4312191347

What Socratic holds

Textmetadata
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 Socratic graph.