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Record W3017010761 · doi:10.1002/pep2.24165

Therapeutic peptides targeting the Ras superfamily

2020· article· en· W3017010761 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

fundA Canadian funder is recorded on the work.
no affNo Canadian affiliation: this work is invisible to an affiliation-only frame.
No Canadian affiliation. An affiliation-only frame, the usual design, would never have seen this work. It is one of the works that make the case for inverting the frame.

Bibliographic record

VenuePeptide Science · 2020
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicProtein Kinase Regulation and GTPase Signaling
Canadian institutionsnot available
FundersMedical Research CouncilMedical Research Council CanadaDepartment of Biochemistry, University of CambridgeBiotechnology and Biological Sciences Research CouncilAstraZeneca
KeywordsRas superfamilyGTPaseSmall moleculeComputational biologyDrug discoverySUPERFAMILYBiologyBioinformaticsCell biologyBiochemistryGeneEnzymeGTP'

Abstract

fetched live from OpenAlex

Abstract The Ras superfamily of small GTPases are master regulators of numerous essential processes within the cell, so that when they malfunction, cancer and many other diseases can result. For example, activating Ras mutations are present in approximately 20% of human cancers. As such, they are key therapeutic targets, yet more than three decades of intensive research efforts have failed to produce effective Ras inhibitors in the clinic. This is, in part, due to their relatively smooth surfaces which are difficult to target through traditional drug discovery methods using small molecules. Peptides offer a solution to this issue as they occupy larger surface areas on their targets and therefore offer exquisite selectivity and affinity. However, their use in the past has been limited to extracellular targets due to delivery issues. Recent advances in peptide macrocyclisation, modifications and delivery methods have ignited increased interest in the use of these highly effective biologics for intracellular targets. This review will cover progress made in the development of peptides targeting small GTPases to treat a wide range of diseases.

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.

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 score0.055
Threshold uncertainty score0.283

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 head0.021
GPT teacher head0.255
Teacher spread0.234 · 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