biostudies-literatureUnknown4(4)Randazzo O<b>Aim:</b> Because mutations of splicing factor 3B subunit-1 (SF3B1) have been identified in 4% of pancreatic ductal adenocarcinoma (PDAC) patients, we investigated the activity of new potential inhibitors of SF3B1 in combination with gemcitabine, one of the standard drugs, in PDAC cell lines. <b>Methods:</b> One imidazo[2,1-<i>b</i>][1,3,4]thiadiazole derivative (IS1) and three indole derivatives (IS2, IS3 and IS4), selected by virtual screening from an in-house library, were evaluated by the sulforhodamine-B and wound healing assay for their cytotoxic and antimigratory activity in the PDAC cells SUIT-2, Hs766t and Panc05.04, the latter harbouring the SF3B1 mutations. The effects on the splicing pattern of proto-oncogene recepteur d'origine nantais (RON) and the gemcitabine transporter hCancer drug resistance (Alhambra, Calif.)904-922https://www.ebi.ac.uk/biostudies/studies/S-EPMC8992438biostudies-literatureSF3B1 modulators affect key genes in metastasis and drug influx: a new approach to fight pancreatic cancer chemoresistance.PMC8992438Pecoraro CCarbone DDiana PPerricone UCascioferro SMAvan AParrino BGiovannetti ERandazzo OIddouch WAPeters GJfalseSF3B1 modulators affect key genes in metastasis and drug influx: a new approach to fight pancreatic cancer chemoresistance.<b>Aim:</b> Because mutations of splicing factor 3B subunit-1 (SF3B1) have been identified in 4% of pancreatic ductal adenocarcinoma (PDAC) patients, we investigated the activity of new potential inhibitors of SF3B1 in combination with gemcitabine, one of the standard drugs, in PDAC cell lines. <b>Methods:</b> One imidazo[2,1-<i>b</i>][1,3,4]thiadiazole derivative (IS1) and three indole derivatives (IS2, IS3 and IS4), selected by virtual screening from an in-house library, were evaluated by the sulforhodamine-B and wound healing assay for their cytotoxic and antimigratory activity in the PDAC cells SUIT-2, Hs766t and Panc05.04, the latter harbouring the SF3B1 mutations. The effects on the splicing pattern of proto-oncogene recepteur d'origine nantais (RON) and the gemcitabine transporter h2021-01-01T00:00:00Z20212025-04-04T19:31:59.266Z2025-02-19T02:57:55.004ZS-EPMC89924383558238110.20517/cdr.2021.61