Abstract 5639: A potent aminosteroid (RM-581) that inhibits orally in mice the tumor growth in an orthotopic xenograft pancreatic cancer model
Bibliographic record
Abstract
Abstract Pancreatic cancer has a very poor prognosis, with a 5-year survival rate of only 10%, making it imperative to develop effective small molecules as new drugs. The aim of this study was to validate the in vitro and in vivo efficacy of a promising endoplasmic reticulum-stress aggravator, the synthetic aminosteroid RM-581, that induces apoptosis, as a potential treatment for pancreatic cancer. When tested on a panel of human (PANC-1, MIACaPa2, L3.6, CAPAN-1, BxPC3) and murine (Pan02) pancreatic cancer cells, RM-581 strongly reduced their proliferation (IC50 = 0.83, 0.45, 2.10, 0.78, 5.75 and 1.77 μM, respectively), which justified its evaluation in a PANC-1-Luc cell-derived orthotopic xenograft model in nu/nu mice. After 5 weeks of oral treatment with RM-581 by gavage (po) daily, in vivo fluorescence imaging (IVIS) imaging showed inhibited tumor growth of 11, 54 and 76% at 10, 40 and 80 mg/kg, respectively, compared to the untreated control group. Compared with a cholesterol biosynthesis inhibitor pravastatin (4 mg/kg/subcutaneous (sc)), the effect of RM-581 was similar at 40 mg/kg/po and greater at 80 mg/kg/po. Inhibitions obtained with RM-581 and pravastatin were also confirmed by tumor weight measurement at necropsy. A comparison with antineoplastic drug docetaxel (4 mg/kg/intraperitoneal/2 x weekly) was however not possible, since several toxicities were found after 2 weeks of treatment, forcing euthanasia of the mice. From histological evaluation (hematoxylin and eosin staining), no differences were found in the liver, kidney and spleen in all groups, which is consistent with the clinical observation of no signs of toxicities and no differences in body weight for RM-581 treatments. In summary, RM-581 is therefore a promising candidate for a possible oral treatment of pancreatic cancer. Citation Format: Donald Poirier, Qi Chen, René Maltais, Jenny Roy, Forkan Ahamed, Shannon Arnold. A potent aminosteroid (RM-581) that inhibits orally in mice the tumor growth in an orthotopic xenograft pancreatic cancer model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5639.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".