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.
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 imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".