A cell-permeable peptide-based PROTAC against the oncoprotein CREPT proficiently inhibits pancreatic cancer
Danhui Ma, Yutian Zou, Yunxiang Chu, Zhengsheng Liu, Gaochao Liu, Jun Chu, Mengdi Li, Jiayu Wang, Shi‐Yong Sun, Zhijie Chang
Abstract
Cancers remain a threat to human health due to the lack of effective therapeutic strategies. Great effort has been devoted to the discovery of drug targets to treat cancers, but novel oncoproteins still need to be unveiled for efficient therapy. Methods: We show that CREPT is highly expressed in pancreatic cancer and is associated with poor disease-free survival. CREPT overexpression promotes but CREPT deletion blocks colony formation and proliferation of pancreatic cancer cells. To provide a proof of concept for CREPT as a new target for the inhibition of pancreatic cancer, we designed a cell-permeable peptide-based proteolysis targeting chimera (PROTAC), named PRTC, based on the homodimerized leucine-zipper-like motif in the C-terminus domain of CREPT to induce its degradation in vivo.