Development of cannabinoid receptor (CB 2 R) ligands for application in PET studies - where to attach the radiolabel?
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
The cannabinoid receptors type 2 (CB2R) are involved in many physiological processes but their expression level in healthy and diseased brain has not been unravelled. With positron emission tomography (PET) it is possible to monitor quantitatively very low amounts of compounds labelled with positron emitting isotopes like 18F in living organisms at high spatial resolution. For application in clinical research, such radiotracers have to show high selectivity and affinity to the target protein. A series of fluorinated N-carbazolyl-oxadiazolyl-propionamides [1] was synthesised and the affinity towards the human CB2R was measured in receptor binding studies. Here, we combine our CB2R receptor model with 3D-QSAR data [2] to support molecular docking studies employing the MOE software (Version 2012.12 Chemical Computing Group Inc. Montreal. http://www.chemcomp.com). The studies revealed that both the primarily investigated compound 2 and the 2-fluoroethyl substituted carbazole derivative 1 (Ki = 3.6 nM) fits well into the binding pocket. Attachment of the fluorine at different positions of the structure does not lead to significantly different poses in accordance with the experimental data. Organ distribution studies on CD1-mice verified our prediction, [3] that [18F]1 and [18F]2 can cross the blood-brain barrier. Figure 1 Compounds 1 and 2 fitted into the binding pocket of the CB2R receptor model.
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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 it