MCULE-8715589337

MCULE-8715589337 is a small molecule inhibitor of the receptor tyrosine kinase-like orphan receptor 1 (ROR1), an onco-embryonic antigen that is highly expressed in various cancers, including pancreatic cancer, but absent in normal adult tissues. Identified through a large-scale structure-based virtual screening of over 10 million compounds, MCULE-8715589337 was found to interact with the ROR1 kinase domain, forming hydrogen bonds with residues such as ASP633, SER632, LYS506, and GLU523. In preclinical evaluations presented at the AACR 2024 meeting, the compound demonstrated antiproliferative activity against MiaPaCa-2 and PANC-1 pancreatic cancer cell lines with IC50 values of approximately 39 μM and 38 μM, respectively. Its stable binding profile and molecular interactions suggest potential for further optimization as a targeted therapy for ROR1-positive malignancies.