XP-524
/ XTRemisBio
- LARVOL DELTA
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October 13, 2025
Dual targeting of BET and EP300 with XP-524 in pancreatic cancer lines resistant to KRAS inhibitors
(AACR-NCI-EORTC 2025)
- " We treated PDAC cell lines, Panc1 and AsPC1, with KRAS-G12D inhibitor (MRTX1133), selecting surviving cells after each passage...The concentration-response of both parent and resistant cell cultures was assayed after treatment with XP-524, pan-KRAS inhibitor (BI-2865), RAS-ON inhibitor (RMC-6236), or KRAS G12D inhibitor (RMC-9805), measuring antiproliferative potency and both mRNA and protein expression... Panc1-MR cells were resistant to all evaluated KRAS inhibitors in clinical development, showing no response to KRAS inhibitors below 1 µM concentration. Small right shifts in concentration-response were seen for all inhibitors in AsPC1-MR cells. XP-524 retained efficacy as an antiproliferative agent in kinase-resistant PDAC cells, with a small right-shift in antiproliferative potency in Panc1-MR cell cultures relative to parental cell lines."
Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • EP300 • KRAS
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