Identifying Simultaneous Matrix Metalloproteinases/Soluble Epoxide Hydrolase Inhibitors
Bibliographic record
Abstract
Matrix metalloproteinase (MMP) and soluble epoxide hydrolase (sEH) have completely unrelated biological functions, however, their dysregulation produce similar effects on biological systems. Based on the similarity in the reported structural requirements for their inhibition, the current study aimed to identify a simultaneous inhibitor for MMP and sEH. Six compounds were identified as potential simultaneous MMP/sEH inhibitors and tested for their capacity to inhibit MMP and sEH. Inhibition of MMP and sEH activity using their endogenous and exogenous substrates was measured by liquid chromatography/mass spectrometry, spectrophotometry and zymography. Two compounds, CTK8G1143 and ONO-4817, were identified to inhibit both MMP and sEH activity. CTK8G1143 and ONO-4817 inhibited the recombinant human sEH activity by an average of 67.4% and 55.2%, respectively. The IC50 for CTK8G1143 and ONO-4817 to inhibit recombinant human sEH were 5.2 and 3.5 µM, respectively, whereas, their maximal inhibition values were 71.4% and 42.8%, respectively. Also, MMP and sEH activity of human cardiomyocytes were simultaneously inhibited by CTK8G1143 and ONO-4817. Regarding other compounds, they showed either MMP or sEH inhibitory activity but not both. In conclusion, these two simultaneous inhibitors of MMP and sEH could provide a promising intervention for the prevention and control of several diseases, especially cardiovascular diseases. This work was supported by a grant from the CIHR to AOSE.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".