The potent quadruplex-binding compound SOP1812 shows anti-tumor activity in patientderived in vivo models of pancreatic cancer

Abstract The compound SOP1812, a tetra-substituted naphthalene diimide derivative has been previously disclosed to have single-digit nM anti-proliferative activity in a panel of human pancreatic ductal adenocarcinoma (PDAC) cell lines (Ahmed et al., ACS Med Chem Lett, 2020, 11, 1634-1644). It also has significant anti-tumor activity in the MIA-PACA2 xenograft model for PDAC as well as in the more demanding KPC model. We now report that this compound also shows significant anti-tumor activity in three patient-derived xenograft (PDX) models for PDAC. One is from a primary PDAC tumor at stage I and the two others from patients with stage IV PDAC (PDX tumor studies undertaken under contract by Champions Oncology). Transcriptome studies on cellular responses to SOP1812 have previously demonstrated that expression of a number of oncogenes and related signaling pathways are down-regulated by this agent. The promoter regions of these genes have an over-representation of quadruplex-containing sequences and several have also been shown by us to be also down-regulated in treated tumor xenografts. Our working hypothesis that the mechanism of action of SOP1812 in vivo involves targeting of quadruplex-containing genes, is also supported by the PDX data since these tumors have elevated levels of several quadruplex-containing genes previously identified by us in cells and in vivo. SOP1812 is bio-available at therapeutic doses and is well tolerated at these levels in these animal models. It is currently being evaluated as a candidate for clinical development by Qualigen Therapeutics Inc. Citation Format: Stephen Neidle, Ahmed Ahmed, Richard Angell, Sally Oxenford. The potent quadruplex-binding compound SOP1812 shows anti-tumor activity in patient-derived in vivo models of pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4069.