Nerve growth factor inhibitor with novel‐binding domain demonstrates nanomolar efficacy in both cell‐based and cell‐free assay systems
Bibliographic record
Abstract
Abstract Nerve growth factor (NGF), a member of the neurotrophin family, is known to regulate the development and survival of a select population of neurons through the binding and activation of the TrkA receptor. Elevated levels ofNGFhave been associated with painful pathologies such as diabetic neuropathy and fibromyalgia. However, completely inhibiting theNGFsignal could hold significant side effects, such as those observed in a genetic condition called congenital insensitivity to pain and anhidrosis (CIPA). Previous methods of screening forNGF‐inhibitors used labeling techniques which have the potential to alter molecular interactions.SPRspectroscopy andNGF‐dependent cellular assays were utilized to identify a novelNGF‐inhibitor,BVNP‐0197 (IC50 = 90 nmol/L), the firstNGF‐inhibitor described with a high nanomolarNGFinhibition efficiency. The present study utilizes molecular modeling flexible docking to identify a novel binding domain in the loopII/IVcleft ofNGF.
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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) | 0.001 | 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) | 0.001 | 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".