PROTAC PLK1 Degrader-2 is a peptide-based N-end rule PLK1 mini-PROTAC. PROTAC PLK1 Degrader-2 utilizes Arg12 as dual-function cell-permeable N-degron to recruit UBR1/UBR2 E3 ligases, mediates PLK1 ubiquitination and proteasome-dependent degradation. PROTAC PLK1 Degrader-2 suppresses cervical cancer cell proliferation, induces G2/M cell cycle arrest and tumor cell apoptosis, and exerts potent in vivo anti-tumor efficacy in mice and can be applied to research on PLK1 -driven cervical carcinoma ( PLK1 ligand: POI ligand-3; E3 ligase ligand: Arg12; PROTAC linker: 6-Aminocaproic acid ) [1].
In Vivo, PROTAC PLK1 Degrader-2 (compound NC1) (4 mg/kg, tail vein injection, every 3-4 days for 29 days) significantly suppresses tumor growth in a HeLa xenograft mouse model, reduced Tumor volume with no significant body weight loss observed[1].
In Vitro, PROTAC PLK1 Degrader-2 (compound NC1) (1-5 μM; 24 h) induces dose-dependent degradation of endogenous PLK1 protein in HeLa cervical cancer cells[1]. PROTAC PLK1 Degrader-2 (5 μM; 24 h) completely loses PLK degradation activity after co-treatment with proteasome inhibitor MG-132 [1]. PROTAC PLK1 Degrader-2 (6 μM; 24 h) induces G2/M phase cell cycle arrest in HeLa cells and effectively penetrates HeLa cell membrane and accumulates in cell nucleus[1]. PROTAC PLK1 Degrader-2 (0.325-12 μM; 24 h) suppresses HeLa cell viability in a concentration-dependent manner with cell proliferation IC50 = 5.23 μM[1]. PROTAC PLK1 Degrader-2 binds recombinant PLK1 PBD protein with a dissociation constant Kd = 6.06 μM[1].
References:
[1]. Gunasekaran P, et al. N-Degron-Based PROTAC Targeting PLK1: A Potential Therapeutic Strategy for Cervical Cancer. Pharmaceutics. 2025 Aug 7;17(8):1027.
In Vivo, PROTAC PLK1 Degrader-2 (compound NC1) (4 mg/kg, tail vein injection, every 3-4 days for 29 days) significantly suppresses tumor growth in a HeLa xenograft mouse model, reduced Tumor volume with no significant body weight loss observed[1].
In Vitro, PROTAC PLK1 Degrader-2 (compound NC1) (1-5 μM; 24 h) induces dose-dependent degradation of endogenous PLK1 protein in HeLa cervical cancer cells[1]. PROTAC PLK1 Degrader-2 (5 μM; 24 h) completely loses PLK degradation activity after co-treatment with proteasome inhibitor MG-132 [1]. PROTAC PLK1 Degrader-2 (6 μM; 24 h) induces G2/M phase cell cycle arrest in HeLa cells and effectively penetrates HeLa cell membrane and accumulates in cell nucleus[1]. PROTAC PLK1 Degrader-2 (0.325-12 μM; 24 h) suppresses HeLa cell viability in a concentration-dependent manner with cell proliferation IC50 = 5.23 μM[1]. PROTAC PLK1 Degrader-2 binds recombinant PLK1 PBD protein with a dissociation constant Kd = 6.06 μM[1].
References:
[1]. Gunasekaran P, et al. N-Degron-Based PROTAC Targeting PLK1: A Potential Therapeutic Strategy for Cervical Cancer. Pharmaceutics. 2025 Aug 7;17(8):1027.