MétaCan
Menu
Back to cohort
Record W2060778947 · doi:10.1021/jm0495069

Synthetic Bryostatin Analogues Activate the RasGRP1 Signaling Pathway

2004· article· en· W2060778947 on OpenAlexaff
James C. Stone, Stacey L. Stang, Yong Zheng, Nancy A. Dower, Stacey E. Brenner, Jeremy L. Baryza, Paul A. Wender

Bibliographic record

VenueJournal of Medicinal Chemistry · 2004
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicProtein Kinase Regulation and GTPase Signaling
Canadian institutionsUniversity of Alberta
FundersNational Cancer Institute
KeywordsChemistryBryostatin 1Signal transductionStereochemistryBiochemistryProtein kinase C

Abstract

fetched live from OpenAlex

The functional properties of four diacylglycerol (DAG) analogues were compared using cell-signaling assays based on the protein RasGRP1, a DAG-regulated Ras activator. Compounds 1 and 2, synthetic analogues of bryostatin 1, were compared to authentic bryostatin 1 and phorbol 12-myristate-13-acetate (PMA). The two "bryologues" were able to activate RasGRP1 signaling rapidly in cultured cells and isolated mouse thymocytes. They elicited expression of the T cell activation marker CD69 in human T cells. DAG analogues promptly recruited RasGRP1 to cell membranes, but they did not induce RasGRP1 proteolysis. Bryostatin 1 and compounds 1 and 2 appeared to be less potent than PMA at inducing aggregation of mouse thymocytes, a PKC-dependent, RasGRP1-independent response. In addition to sharing potential anticancer properties with bryostatin 1, compounds 1 and 2 might be clinically useful as modulators of the immune system.

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)0.001
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 score0.009
Threshold uncertainty score0.405

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
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 head0.010
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 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
Published2004
Admission routes1
Has abstractyes

Explore more

Same venueJournal of Medicinal ChemistrySame topicProtein Kinase Regulation and GTPase SignalingFrench-language works237,207