A new article published in BIO Integration on Jul. 7 announces the identification of a potential compound for pancreatic cancer treatment. Researchers evaluated fat mass and obesity-associated protein (FTO), an epitranscriptomic regulator implicated in cancer progression and immune regulation, to determine its therapeutic relevance in pancreatic cancer.
The study analyzed transcriptomic datasets from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) projects to assess FTO expression levels and their association with prognosis in pancreatic cancer patients. Candidate compounds targeting FTO were identified using active learning-assisted virtual screening of more than 22 million molecules.
The lead candidate, DE19725241, was further examined through binding pose metadynamics, molecular dynamics simulations across various environments, MM/GBSA calculations, and laboratory testing on three pancreatic cancer cell lines as well as one normal pancreatic epithelial cell line. The findings showed that FTO was overexpressed in pancreatic tumors and correlated with poorer overall survival rates.
DE19725241 demonstrated favorable predicted interactions with the FTO protein—specifically at ARG-96, TYR-108, and GLU-234 residues—and exhibited moderate but selective antiproliferative activity against pancreatic cancer cells. According to the publication, "DE19725241 represents a potential early-stage scaffold for developing FTO-targeted strategies in pancreatic cancer."
