Spiropyrrolizidine and piperazine derivatives: Synthesis and evaluation on kras expression levels in human colon cancer cells
Bibliographic record
Abstract
KRAS-driven cancers are notoriously difficult to treat due to poor pharmacodynamics of downstream inhibitors and resistance to anti-EGFR drugs. IMP-1 is a post-transcriptional regulator of KRAS mRNA. As a novel therapeutic approach, the targeting of the IMP-1-KRAS mRNA complex with a spiropyrrolizidine derivative (UNBC152), was studied. LC-MS analysis of UNBC152 indicated presence of impurities. The purpose of this study was to synthesize UNBC152 and determine the responsible bioactive molecule within the impurities. LC-MS and TLC suggested the presence of a bioactive [3+3] cycloaddition side product (SPOPP) in UNBC152. SPOPP suppressed KRAS expression in human colorectal cancer cells. Fluorescence polarization determined that SPOPP did not impact the IMP-1-KRAS mRNA interaction. SPOPP induced G2/M cell cycle arrest as shown by flow cytometry. MTT assay confirmed the SPOPP-induced growth inhibition in SW480 (IC50 = 4.17 μM) and HT29 (IC50 = 6.76 μM). These findings represent a first reporting on the bioactivity of SPOPP.
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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 | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".