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Record W2887597537 · doi:10.1021/acs.jmedchem.8b01045

Design, Synthesis, and Biological Evaluation of 3-(Imidazo[1,2-<i>a</i>]pyrazin-3-ylethynyl)-4-isopropyl-<i>N</i>-(3-((4-methylpiperazin-1-yl)methyl)-5-(trifluoromethyl)phenyl)benzamide as a Dual Inhibitor of Discoidin Domain Receptors 1 and 2

2018· article· en· W2887597537 on OpenAlexfundno aff
Zhen Wang, Yali Zhang, Daniel M. Pinkas, Alice E. Fox, Jinfeng Luo, Huocong Huang, Shengyang Cui, Qiuping Xiang, Tingting Xu, Qiuju Xun, Dongsheng Zhu, Zhengchao Tu, Xiaomei Ren, Rolf A. Brekken, Alex N. Bullock, Guang Liang, Ke Ding, Xiaoyun Lu

Bibliographic record

VenueJournal of Medicinal Chemistry · 2018
Typearticle
Languageen
FieldMedicine
TopicCell Adhesion Molecules Research
Canadian institutionsnot available
FundersStructural Genomics ConsortiumJinan UniversityNational Natural Science Foundation of ChinaWellcome TrustWellcome
KeywordsChemistryBenzamideIn vivoLead compoundDDR1KinasePharmacologyDiscoidin domainIn vitroJurkat cellsIC50Drug discoveryStereochemistryBiochemistryReceptor tyrosine kinaseImmunology

Abstract

fetched live from OpenAlex

values of 9.4 and 20.4 nM, respectively; and was significantly less potent for a panel of 403 wild-type kinases at 1.0 μM. DDR1- and DDR2-kinase inhibition by 5n was validated by Western-blotting analysis in primary human lung fibroblasts. The compound also dose-dependently inhibited lipopolysaccharide (LPS)-induced interleukin 6 (IL-6) release in vitro and exhibited promising in vivo anti-inflammatory effects in an LPS-induced-acute-lung-injury (ALI) mouse model. Compound 5n may serve as a lead compound for new anti-inflammatory drug discovery.

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)0.010
metaresearch head score (Gemma)0.009
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMetaresearch, Meta-epidemiology (narrow), Insufficient payload (model declined to judge)
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
Metaresearch0.0100.009
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0000.002
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

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 head0.045
GPT teacher head0.336
Teacher spread0.292 · 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

Citations31
Published2018
Admission routes1
Has abstractyes

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