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Targeted degradation of Pin1 by an antagonistic peptide enhances gemcitabine therapy in pancreatic cancer.

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RSC medicinal chemistry 📖 저널 OA 100% 2024: 2/2 OA 2025: 18/18 OA 2026: 20/20 OA 2024~2026 2025
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Chen M, Chu X, Zhao H, Ma L, Meng J, Yang Y

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Targeted protein degradation (TPD) has emerged as a powerful strategy for eliminating disease-causing proteins.

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↓ .bib ↓ .ris
APA Chen M, Chu X, et al. (2025). Targeted degradation of Pin1 by an antagonistic peptide enhances gemcitabine therapy in pancreatic cancer.. RSC medicinal chemistry. https://doi.org/10.1039/d5md00970g
MLA Chen M, et al.. "Targeted degradation of Pin1 by an antagonistic peptide enhances gemcitabine therapy in pancreatic cancer.." RSC medicinal chemistry, 2025.
PMID 41574233 ↗
DOI 10.1039/d5md00970g

Abstract

Targeted protein degradation (TPD) has emerged as a powerful strategy for eliminating disease-causing proteins. The prolyl isomerase Pin1 is an attractive therapeutic target given its oncogenic function. Here, we develop PIPWF, a novel peptide degrader that induces Pin1 degradation through multivalent binding and conformational destabilization. Pin1 degradation attenuates cancer-associated fibroblast (CAF) activation to reshape the fibrotic tumor microenvironment and enhance chemosensitivity ENT1-mediated gemcitabine uptake. results demonstrated that both PIPWF and its nanoformulation M-PIPWF synergized with gemcitabine to induce tumor regression and prolong survival, illustrating a novel peptide-based TPD strategy against Pin1-driven malignancies.

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