Evidence map›Paper›PMID 33800546›Full record

ArticleInternational journal of molecular sciences2021

Diphenyl-Methane Based Thyromimetic Inhibitors for Transthyretin Amyloidosis.

Bokyung Kim, Young Ho Ko, Massimiliano Runfola, Simona Rapposelli, Gabriella Ortore, Grazia Chiellini, Jin Hae Kim

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.5field-weighted citation impact, top 39% 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

7 citing papers in PubMed, 8 citations in OpenAlex.

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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

7 authors at 3 institutions in 2 countries.

Bokyung KimDepartment of New Biology, Daegu Gyeongbuk Institute of Science & Technology (DGIST), Daegu 42988, Korea.
Young Ho KoCenter for Self-Assembly and Complexity, Institute for Basic Science, Pohang 37673, Korea.
Massimiliano RunfolaDepartment of Pharmacy, University of Pisa, 56100 Pisa, Italy.ORCID 0000-0002-3608-2031
Simona RapposelliDepartment of Pharmacy, University of Pisa, 56100 Pisa, Italy.ORCID 0000-0003-0146-6358
Gabriella OrtoreDepartment of Pharmacy, University of Pisa, 56100 Pisa, Italy.
Grazia ChielliniDepartment of Pathology, University of Pisa, 56100 Pisa, Italy.ORCID 0000-0001-6703-5820
Jin Hae KimDepartment of New Biology, Daegu Gyeongbuk Institute of Science & Technology (DGIST), Daegu 42988, Korea.ORCID 0000-0002-6776-2451
University of Pisa · ITDaegu Gyeongbuk Institute of Science and Technology · KRInstitute for Basic Science · KR

Funding

Institute for Basic Science IBS-R007-D1National Research Foundation of Korea NRF-2018R1C1B6008282
6 · The paper itself

Abstract

Thyromimetics, whose physicochemical characteristics are analog to thyroid hormones (THs) and their derivatives, are promising candidates as novel therapeutics for neurodegenerative and metabolic pathologies. In particular, sobetirome (GC-1), one of the initial halogen-free thyromimetics, and newly synthesized IS25 and TG68, with optimized ADME-Tox profile, have recently attracted attention owing to their superior therapeutic benefits, selectivity, and enhanced permeability. Here, we further explored the functional capabilities of these thyromimetics to inhibit transthyretin (TTR) amyloidosis. TTR is a homotetrameric transporter protein for THs, yet it is also responsible for severe amyloid fibril formation, which is facilitated by tetramer dissociation into non-native monomers. By combining nuclear magnetic resonance (NMR) spectroscopy, computational simulation, and biochemical assays, we found that GC-1 and newly designed diphenyl-methane-based thyromimetics, namely IS25 and TG68, are TTR stabilizers and efficient suppressors of TTR aggregation. Based on these observations, we propose the novel potential of thyromimetics as a multi-functional therapeutic molecule for TTR-related pathologies, including neurodegenerative diseases.

Indexed as

AcetatesAmyloidAmyloid Neuropathies, FamilialBenzothiazolesBiphenyl CompoundsDrug DesignHumansMagnetic Resonance SpectroscopyMethaneMolecular Docking SimulationMolecular Dynamics SimulationPermeabilityPhenolsPrealbuminProtein BindingProtein FoldingAcetatesAmyloidBenzothiazolesbiphenylBiphenyl CompoundsGC 1 compoundMethanePhenolsPrealbuminRecombinant Proteinsthioflavin TThyroid Hormonesprotein aggregationsobetiromethyromimeticstransthyretinTTR amyloidosisTTR stabilizers

Identifiers

PMID33800546
PMCPMC8038088
OpenAlexW3146944433

What OpenQuestion holds

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LicenceCC BY
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.