A cell-permeable peptide-based PROTAC against the oncoprotein CREPT proficiently inhibits pancreatic cancer

摘要: Cancers remain a threat to human health due the lack of effective therapeutic strategies. Great effort has been devoted discovery drug targets treat cancers, but novel oncoproteins still need be unveiled for efficient therapy. Methods: We show that CREPT is highly expressed in pancreatic cancer and associated with poor disease-free survival. overexpression promotes deletion blocks colony formation proliferation cells. To provide proof concept as new target inhibition cancer, we designed cell-permeable peptide-based proteolysis targeting chimera (PROTAC), named PRTC, based on homodimerized leucine-zipper-like motif C-terminus domain induce its degradation vivo. Results: PRTC high affinity CREPT, Kd = 0.34 +/- 0.11 μM able permeate into cells because attached membrane-transportable peptide RRRRK. effectively induces proteasome-dependent manner. Intriguingly, inhibits formation, cell proliferation, motility ultimately impairs xenograft tumor growth, comparable effect deletion. Conclusions: PRTC-induced leads which promising development drugs against cancer. In addition, using an interacting dimerized structure proteins may way design PROTAC aiming at degrading any protein without known small molecules or peptides.