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Record W3004879944 · doi:10.1038/s41467-019-14091-4

Inhibition of vascular calcification by inositol phosphates derivatized with ethylene glycol oligomers

2020· article· en· W3004879944 on OpenAlexafffund
Antonia E. Schantl, Anja Verhulst, Ellen Neven, Geert J. Behets, Patrick C. D’Haese, Marc Maillard, David Mordasini, Olivier Phan, Michel Burnier, Dany Spaggiari, Laurent A. Décosterd, Mark G. MacAskill, Carlos J. Alcaide‐Corral, Adriana Tavares, David E. Newby, Victoria C. Beindl, Roberto Maj, Anne Labarre, Chrismita Hegde, Bastien Castagner, Mattias E. Ivarsson, Jean‐Christophe Leroux

Bibliographic record

VenueNature Communications · 2020
Typearticle
Languageen
FieldMedicine
TopicParathyroid Disorders and Treatments
Canadian institutionsMcGill University
FundersBranco Weiss Fellowship – Society in ScienceInnosuisse - Schweizerische Agentur für InnovationsförderungÉcole Polytechnique Fédérale de LausanneNatural Sciences and Engineering Research Council of CanadaBritish Heart Foundation
KeywordsInositolCalcificationChemistryInositol phosphateIn vitroCalciumPhosphatePharmacokineticsBiochemistryToxicityPharmacologyInternal medicineBiologyMedicineReceptor

Abstract

fetched live from OpenAlex

Abstract Myo -inositol hexakisphosphate (IP6) is a natural product known to inhibit vascular calcification (VC), but with limited potency and low plasma exposure following bolus administration. Here we report the design of a series of inositol phosphate analogs as crystallization inhibitors, among which 4,6-di- O -(methoxy-diethyleneglycol)- myo -inositol-1,2,3,5-tetrakis(phosphate), (OEG 2 ) 2 -IP4, displays increased in vitro activity, as well as more favorable pharmacokinetic and safety profiles than IP6 after subcutaneous injection. (OEG 2 ) 2 -IP4 potently stabilizes calciprotein particle (CPP) growth, consistently demonstrates low micromolar activity in different in vitro models of VC (i.e., human serum, primary cell cultures, and tissue explants), and largely abolishes the development of VC in rodent models, while not causing toxicity related to serum calcium chelation. The data suggest a mechanism of action independent of the etiology of VC, whereby (OEG 2 ) 2 -IP4 disrupts the nucleation and growth of pathological calcification.

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 score0.106
Threshold uncertainty score0.410

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 head0.017
GPT teacher head0.289
Teacher spread0.272 · 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

Citations54
Published2020
Admission routes2
Has abstractyes

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