Orally active aminosteroid RM-581 suppresses tumor growth and metastasis formation in a gemcitabine-resistant orthotopic xenograft pancreatic cancer model
Year: 2026
Type: article
Abstract: New agents with distinct mechanisms of action are urgently needed to overcome drug resistance and improve survival, particularly in highly lethal cancers. The estrane derivative RM-581, designed through structure–activity relationship studies, needed to demonstrate efficacy in poor-prognosis cancer models, such as pancreatic cancer, to validate its therapeutic potential. Oral administration of RM-581 (30 mg/kg) in female mice revealed improved pharmacokinetic parameters (C max , AUC, bioavailability) when formulated in Propylene glycol: DMSO, compared with Glycerol: DMSO. Plasma levels of RM-581 increased dose-dependently, and once-daily dosing produced exposure comparable to twice-daily administration. In an orthotopic PANC-1 human pancreatic cancer xenograft model with female nu/nu mice, orally administered RM-581 inhibited tumor growth in a dose-dependent manner by 11%, 54%, and 74% at 10, 40 and 80 mg/kg, respectively. RM-581 at 80 mg/kg suppressed tumor growth by 74–95% and prevented metastasis, whereas 33% of control mice developed metastatic lesions. The combination of RM-581 with Pravastatin also prevented metastasis. RM-581 was well tolerated during 35- and 48-day treatment periods, with no clinical signs of toxicity, including stable body weight, normal organ appearance, unremarkable histopathology, and normal animal behavior, indicating a favorable safety profile. Together, these findings position RM-581 as a promising preclinical candidate warranting advancement into clinical development.
Source: Scientific Reports
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,690
OpenAlex ID: W7225006608