Discovery of Novel P2Y14 Agonist and Antagonist Using Conventional and Nonconventional Methods
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
P2Y14 is a member of the pyrimidinergic GPCR family. UDP-Glc has been previously shown to activate human P2Y14, whereas UDP was unable to activate the receptor. In this study, the authors used conventional and nonconventional methods to further characterize P2Y14 and its ligands. Conventional calcium mobilization and nonconventional cellular impedance functional assays revealed that UMP and UDP selectively activated HEK cells coexpressing P2Y14 and Gαqi5. In the impedance assays, the presence of exogenous Gαqi5 resulted in agonist-induced Gq signaling, whereas in the absence of exogenous Gαqi5, the signal was indicative of Gi. The authors established the first P2Y14 membrane filtration binding assay using a novel optimized expression vector and [3H]UDP as radioligand. UDP-Glc, UMP, and UDP dose dependently inhibited [3H]UDP binding in the binding assay, and saturation analysis revealed that UDP bound P2Y14 with a KD = 10 nM and a Bmax = 110 pmol/mg. The authors screened a phosphonate library and identified compound A, which inhibited UDP-Glc–mediated calcium signaling in the fluorometric imaging plate reader assay (IC50 = 2.3 µM) and competed for [3H]UDP binding in the novel binding assay with a Ki = 1280 nM. P2Y14 is a member of the pyrimidinergic GPCR family. UDP-Glc has been previously shown to activate human P2Y14, whereas UDP was unable to activate the receptor. In this study, the authors used conventional and nonconventional methods to further characterize P2Y14 and its ligands. Conventional calcium mobilization and nonconventional cellular impedance functional assays revealed that UMP and UDP selectively activated HEK cells coexpressing P2Y14 and Gαqi5. In the impedance assays, the presence of exogenous Gαqi5 resulted in agonist-induced Gq signaling, whereas in the absence of exogenous Gαqi5, the signal was indicative of Gi. The authors established the first P2Y14 membrane filtration binding assay using a novel optimized expression vector and [3H]UDP as radioligand. UDP-Glc, UMP, and UDP dose dependently inhibited [3H]UDP binding in the binding assay, and saturation analysis revealed that UDP bound P2Y14 with a KD = 10 nM and a Bmax = 110 pmol/mg. The authors screened a phosphonate library and identified compound A, which inhibited UDP-Glc–mediated calcium signaling in the fluorometric imaging plate reader assay (IC50 = 2.3 µM) and competed for [3H]UDP binding in the novel binding assay with a Ki = 1280 nM.
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.
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 | 0.000 | 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 | 0.000 |
| 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 it