Gunasekaran, Pethaiah Shin, Sang Chul Hwang, Yeon Sil Lee, Jihyeon La, Yeo Kyung Yim, Min Su Kim, Hak Nam Kim, Tae Wan Yang, Eunjung Lee, Soo Jae Yoon, Jung Min Kim, Eunice EunKyeong Jeon, Seob Ryu, Eun Kyoung Bang, Jeong Kyu 2025-08-31T01:30:20Z 2025-08-31T01:30:20Z 2025-08-27 2025-08 https://pubs.kist.re.kr/handle/201004/153060 Background: Cervical cancer remains a major global health concern, with existing chemotherapy facing limited effectiveness owing to resistance. Polo-like kinase 1 (PLK1) overexpression in cervical cancer cells is a promising target for developing novel therapies to overcome chemoresistance and improve treatment efficacy. Methods: In this study, we developed a novel PROTAC, NC1, targeting PLK1 PBD via the N-end rule pathway. Results: This PROTAC effectively depleted the PLK1 protein in HeLa cells by inducing protein degradation. The crystal structure of the PBD-NC1 complex identified key PLK1 PBD binding interactions and isothermal titration calorimetry (ITC) confirmed a binding affinity of 6.06 ？M between NC1 and PLK1 PBD. NC1 significantly decreased cell viability with an IC50 of 5.23 ？M, induced G2/M phase arrest, and triggered apoptosis in HeLa cells. In vivo, NC1 suppressed tumor growth in a HeLa xenograft mouse model. Conclusions: This research highlights the potential of N-degron-based PROTACs targeting the PLK1 protein in cancer therapies, highlighting their potential in future cervical anticancer treatment strategies. English Multidisciplinary Digital Publishing Institute (MDPI) N-Degron-Based PROTAC Targeting PLK1: A Potential Therapeutic Strategy for Cervical Cancer Article 10.3390/pharmaceutics17081027 1 Pharmaceutics, v.17, no.8, pp.1027 Pharmaceutics 17 8 1027 Y scie scopus 001557511800001 Pharmacology & Pharmacy Pharmacology & Pharmacy Article POLO-BOX DOMAIN UBIQUITIN LIGASES IDENTIFICATION DEGRADATION INHIBITORS CISPLATIN COMPLEX GROWTH PLK1 PROTAC N-end rule pathway anticancer N-degron