Lanthanide containing compounds for therapeutic care in bone resorption disorders
Why this work is in the frame
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Bibliographic record
Abstract
Lanthanide ions, Ln(III), are known functional mimics of Ca(II) ions and have been shown to affect the bone remodeling cycle. Exploiting this disruption to the bone remodeling cycle has potential for the treatment of bone density disorders, such as osteoporosis. In an effort to find new orally active agents for these disorders, a series of Ln(III) containing complexes incorporating small, non-toxic, bidentate pyrone and pyridinone ligands have been synthesized and characterized (LnL(3), Ln = La, Eu, Gd, Tb, Yb, L = 3-oxy-2-methyl-4-pyrone (ma(-)), 3-oxy-2-ethyl-4-pyrone (ema(-)), 3-oxy-1,2-dimethyl-4-pyridinone (dpp(-)) and 3-oxy-2-methyl-4(1H)-pyridinone (mpp(-))). Preliminary biological analysis included cytotoxicity, cell uptake and bidirectional transport studies in Caco-2 cells and in vitro hydroxyapatite (HA) binding studies. The proportion of intact compounds bound to HA was calculated based on determination of Ln(III) concentration by ICP-MS and by UV-vis spectrophotometric assay of the proligand in solution. The LnL(3) species were found to have IC(50) values at least 6 times greater than that of cisplatin, >or= 98% HA-binding capacity, and permeability coefficients in the moderate range. La(dpp)(3) was ascertained to be the lead compound for the treatment of bone density disorders with the highest percentage cell uptake of 9.07 +/- 2.33% and the highest preliminary P(app) value of 3.54 +/- 2.86 x 10(-6) cm s(-1) compared to the other LnL(3) complexes tested.
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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 | 0.000 | 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