Discovery of 1-phenyl-1,2,3-triazole ureas as dual VEGFR-2/JNK-1 type II kinase inhibitors targeting pancreatic cancer

<p> In oncology, pancreatic cancer (PC) continues to be a problem that requires creative approaches to therapy. This research aims to create dual kinase inhibitors that target VEGFR-2 and JNK-1, two important factors in the angiogenesis and progression of PC. We found compounds with promising anticancer action using phenyltriazolyl piperazine/(piperidine) carboxamides (PTPCs) and phenyltriazolyl phenylureas (PTPUs). Compound 12b was the most effective in inhibiting VEGFR-2 (IC50: 46 nM) and JNK-1 (IC50: 35 nM) and showed the highest activity against PANC-1 cancer cells (IC50: 1.05 μM). Furthermore, 12b altered the caspase-3, Bcl-2, and Bax apoptotic markers. The binding interactions of 12b with target kinases were discovered by <em>in silico</em> investigations. This study emphasizes how dual kinase inhibitors may be a viable way to improve the effectiveness of cancer treatments and deal with resistance mechanisms. </p>