A new class of compound for pancreatic carcinoma targeting the tyrosine kinase receptor (TKR) ROR1.

e13561 Background: There is a medical need to develop novel compounds for treatment of pancreatic carcinoma. Members of the TKR families are attractive therapeutic candidates. One of the families is ROR receptors. ROR1 is of importance during embryogenesis but down-regulated in most adult human tissues. ROR1 has been shown to be overexpressed in hematological malignancies and solid tumors as pancreatic carcinoma. ROR1 siRNA transfection of CLL cells and pancreatic carcinoma cells induced apoptosis. Antibodies against the CRD region of ROR1 evoked specific apoptosis of CLL cells and dephosphorylation of ROR1 (PLOS One 8(10) e78339, 2013). In the present report we have explored the activity of a new class of compound, ROR1 tyrosine kinase inhibitors (ROR1-TKI), inhibiting phosphorylation of the TK domain of ROR1. Methods: ROR1 kinase inhibitorswere derived from a high-through-put screening (HTS) using HTRF assay based on recombinant intracellular kinase domain of ROR1. One chemical lead series was optimized...