Identification of Potent and Selective Human Ecto-Nucleotide Pyrophosphatase/ Phosphodiesterase-3 (hNPP3) Inhibitors
Bibliographic record
Abstract
NPP3 inhibitors are promising therapeutic agents due to their potential as anti-cancer, anti-metastatic and anti-neurodegenerative drugs.We have identified the first potent and selective inhibitors of human NPP3.We have also estimated the biochemical properties of the main NPP family members that can hydrolyse nucleotides using p-nitrophenyl-5'-thymidine monophosphate as substrate.K m values were found to be 20 ± 4 and 15 ± 6 M for human NPP1 and NPP3, respectively.Maximum velocity (V max ) values calculated for NPP1 and NPP3 were 12 ± 2 and 5 ± 1 nmol p-nitrophenol released/min/mg of crude protein, respectively.A series of benzothiazole derivatives and a series of 1,3,4-oxadiazole-2-thiones was tested on hNPP1 and hNPP3.Benzothiazoles were the most potent non competitive inhibitors of hNPP3 described to date.1,3,4-oxadiazole-2-thiones were also identified as compounds which inhibited specifically NPP3 over NPP1.The most potent compound was further characterized and found to exhibit a non competitive mechanism of inhibition.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 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".