Design of anti-allergic inhibitors for human hematopoietic prostaglandin D synthase
Bibliographic record
Abstract
Choline kinase (ChoK) catalyzes the ATP-dependent phosphorylation of choline, the first committed step in the CDP-choline pathway for the biosynthesis of phosphatidylcholine.Overexpression and increased activity of one of the human ChoK isoforms, ChoK alpha have been constitutively reported in malignant cells and tumour tissues.This suggests that the enzyme plays a relevant role in tumorigenesis.Some sets of in vitro and in vivo experiments confirmed that ChoK inhibition is one of the potential novel strateges for the development of new antiproliferative and anticancer drugs.The importance of ChoK for the regulation of cell proliferation has been studied by using an inhibitor hemicholinium-3 (HC-3), which was initially characterized as a lethal, respiratory paralytic agent.Most of the ChoK inhibitors introduced so far are the chemically modified derivatives based on the structure of HC-3.Crystal structures of HC-3 bound human ChoK alpha were determinded with and without ADP.In the crystal structures, HC-3 molecule was well accommodated between the N and C-terminal lobes of ChoK protein, and its one end was placed on the same binding site as a substrate choline, while the other end partially exposed to the solvent.The inhibitor molecule was stabilized mainly through the hydrophobic interactions contributed by the C-terminal lobe.These 3D information provides the first molecular detailed view concerning the mode of inhibitory action and expand our understanding of the factors governing selectivity.
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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 | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".