Data from A Preclinical Evaluation of SKLB261, a Multikinase Inhibitor of EGFR/Src/VEGFR2, as a Therapeutic Agent against Pancreatic Cancer

• DOI: 10.1158/1535-7163.c.6537642.v1
• Publication Date: 2024-03-12T16:57:53Z
• Authors: Youli Pan; Mingwu Zheng; Lei Zhong; Jiao Yang; Shu Zhou; Ya Qin; Rong Xiang; Yuzong Chen; Sheng-Yong Yang
• Keywords: EGFR Inhibitors

<div>Abstract<p>The clinical prognosis of pancreatic cancer remains rather disappointing despite tremendous efforts in exploring medical treatments the past two decades. Development more effective treatment strategies is still desperately needed to improve outcomes patients with cancer. SKLB261 a multikinase inhibitor obtained recently through lead optimization. In this investigation, we shall evaluate its anti–pancreatic effects both <i>in vitro</i> and vivo</i>. potently inhibiting EGFR, Src, VEGFR2 kinases. It could significantly inhibit cell proliferation, migration, invasion, induce apoptosis cellular assays human cells that are sensitive or resistant dasatinib and/or gemcitabine. Western blot analysis showed inhibited activation EGFR Src kinases as well their downstream signaling proteins, including FAK, ERK, STAT3. also potent antiangiogenic transgenic zebrafish models. <i>In vivo</i>, displayed antitumor activities than dasatinib, gemcitabine, erlotinib xenografts, BxPC-3, PANC-1, AsPC-1, HPAC. Furthermore, mice receiving therapy significant survival advantage compared vehicle-treated gemcitabine-treated groups an experimental metastasis model These data, together good pharmacokinetic properties low toxicity compound, provide rationale for ongoing evaluation <i>Mol Cancer Ther; 14(2); 407–18. ©2014 AACR</i>.</p></div>