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Record W4405441258 · doi:10.1021/jacs.4c13558

Photoswitchable Diazocine Derivative for Adenosine A<sub>3</sub> Receptor Activation in Psoriasis

2024· article· en· W4405441258 on OpenAlexfundno aff
Marc López‐Cano, Mirko Scortichini, Dilip K. Tosh, Veronica Salmaso, Tongil Ko, Glòria Salort, Ingrid Filgaira, Concepció Soler, Dirk Trauner, Jordi Hernando, Kenneth A. Jacobson, Francisco Ciruela

Bibliographic record

VenueJournal of the American Chemical Society · 2024
Typearticle
Languageen
FieldMaterials Science
TopicPhotochromic and Fluorescence Chemistry
Canadian institutionsnot available
FundersNextGenerationEUFaculty of Medicine and Health, University of SydneyNational Institutes of HealthGeneralitat de CatalunyaEuropean CommissionNational Institute of Diabetes and Digestive and Kidney DiseasesCentres de Recerca de CatalunyaUniversitat Autònoma de BarcelonaUniversitat de BarcelonaUniversity of PennsylvaniaYork UniversityMinisterio de Ciencia, Innovación y Universidades
KeywordsChemistryAgonistPhotoswitchIn vivoMoietyAdenosineBiophysicsReceptorIn vitroDerivative (finance)StereochemistryBiochemistryPhotochemistry

Abstract

fetched live from OpenAlex

High Resolution Image Download MS PowerPoint Slide Incorporating photoisomerizable moieties within drugs offers the possibility of rapid and reversible light-dependent switching between active and inactive configurations. Here, we developed a photoswitchable adenosine A 3 receptor (A 3 R) agonist that confers optical control on this G protein-coupled receptor through noninvasive topical skin irradiation in an animal model of psoriasis. This was achieved by covalently bonding an adenosine-5′-methyluronamide moiety to a diazocine photochrome, whose singular photoswitching properties facilitated repeated interconversion between a thermally stable, biologically inactive Z agonist form and a photoinduced, pharmacologically active E configuration. As a result, our photoswitchable agonist allowed the precise modulation of A 3 R function both in vitro and in vivo, which led to a clear light-controlled pharmacotherapeutic effect on mouse skin lesions. This breakthrough not only demonstrates the potential of diazocine photoswitches for in vivo photopharmacology but also paves the way for the development of new strategies for skin-related diseases that require localized and temporally controlled drug action.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.018
Threshold uncertainty score0.387

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.011
GPT teacher head0.253
Teacher spread0.242 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations23
Published2024
Admission routes1
Has abstractyes

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Same venueJournal of the American Chemical SocietySame topicPhotochromic and Fluorescence ChemistryFrench-language works237,207