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Record W4394995880 · doi:10.1002/cmdc.202400013

Lysophosphatidic Acid Receptor 1 (LPA<sub>1</sub>) Antagonists as Potential Migrastatics for Triple Negative Breast Cancer

2024· article· en· W4394995880 on OpenAlexafffund
Wenjie Liu, Amr A. K. Mousa, Austin M. Hopkins, Yin Fang Wu, Kelsie L. Thu, Michael J. Campbell, Simon J. Lees, Rithwik Ramachandran, Jinqiang Hou

Bibliographic record

VenueChemMedChem · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicSphingolipid Metabolism and Signaling
Canadian institutionsNOSM UniversitySt. Michael's HospitalWestern UniversityLakehead UniversityUniversity of TorontoThunder Bay Regional Research Institute
FundersNatural Sciences and Engineering Research Council of CanadaLakehead University
KeywordsLysophosphatidic acidTriple-negative breast cancerMetastasisCancer researchCancerBreast cancerCancer cellMetastatic breast cancerChemistryMedicinePharmacologyReceptorInternal medicine

Abstract

fetched live from OpenAlex

Abstract Metastasis is responsible for about 90 % of cancer deaths. Anti‐metastatic drugs, termed as migrastatics, offer a distinctive therapeutic approach to address cancer migration and invasion. However, therapeutic exploitation of metastasis‐specific targets remains limited, and the effective prevention and suppression of metastatic cancer continue to be elusive. Lysophosphatidic acid receptor 1 (LPA 1 ) is activated by an endogenous lipid molecule LPA, leading to a diverse array of cellular activities. Previous studies have shown that the LPA/LPA 1 axis supports the progression of metastasis for many types of cancer. In this study, we report the synthesis and biological evaluation of fluorine‐containing triazole derivatives as potent LPA 1 antagonists, offering potential as migrastatic drugs for triple negative breast cancer (TNBC). In particular, compound 12 f , the most potent and highly selective in this series with an IC 50 value of 16.0 nM in the cAMP assay and 18.4 nM in the calcium mobilization assay, inhibited cell survival, migration, and invasion in the TNBC cell line. Interestingly, the compound did not induce apoptosis in TNBC cells and demonstrated no cytotoxic effects. These results highlight the potential of LPA 1 as a migrastatic target. Consequently, the LPA 1 antagonists developed in this study hold promise as potential migrastatic candidates for TNBC.

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 categoriesMeta-epidemiology (narrow)
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 score1.000

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 head0.007
GPT teacher head0.257
Teacher spread0.250 · 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.

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

Citations2
Published2024
Admission routes2
Has abstractyes

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