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Record W4315698938 · doi:10.3390/ecmc2022-12906

Prodrugs Activated by Vascular Ectopeptidases: Proof of Concept

2022· article· en· W4315698938 on OpenAlexaff
François Marceau

Bibliographic record

VenueECMC 2022 · 2022
Typearticle
Languageen
FieldMedicine
TopicCoagulation, Bradykinin, Polyphosphates, and Angioedema
Canadian institutionsUniversité Laval
Fundersnot available
KeywordsBradykininReceptorVascular smooth muscleHistamineProdrugChemistryPharmacologyAngiotensin IIEndocrinologyInternal medicineBiochemistryBiologyMedicine

Abstract

fetched live from OpenAlex

Several vascular ectopeptidases reside in blood vessels and efficiently regulate peptide hormones. For instance, bradykinin (BK) is inactivated by angiotensin converting enzyme (ACE) or arginine-carboxypeptidases (Arg-CPs), and aminopeptidase N (APN) cleaves several substrates. Whether such peptidases may activate latent prodrugs of vasoactive agents has been tested. The contractility of the isolated human umbilical vein, radioligand binding assays, immunolocalization of peptidases, the internalization cycle of fluorescent receptors (microscopy), blood pressure measurements in anesthetized rats, and specific inhibitors of peptidases have been exploited to show the feasibility of prodrug activation by vascular peptidases. L-alanyl-histamine has virtually no affinity for the human histamine H1 receptor, but releases histamine and contracts the vein following cleavage by endogenous APN. Prolonged sequences of BK, such as BK-Arg, Arg0-BK-Arg-Arg, and BK-His-Leu have little affinity for the BK B2 receptor, but are contractile in the umbilical vein and hypotensive in anesthetized rats via their action on this receptor type following cleavage of the C-terminal extensions by Arg-CPs for the first two peptides, as well as by ACE for the last two. Vascular ectopeptidases were shown to activate latent agonists of the H1 and B2 receptors, a concept that could be extended to various classes of drugs for a local action on the vasculature.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.002
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0010.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.001

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 head0.010
GPT teacher head0.239
Teacher spread0.229 · 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 source (direct Gemma or distilled Codex), 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

Citations0
Published2022
Admission routes1
Has abstractyes

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