Article
Chemistry, Medicinal
SeongShick Ryu, Jung-Eun Park, Young Jin Ham, Daniel C. Lim, Nicholas P. Kwiatkowski, Do-Hee Kim, Debabrata Bhunia, Nam Doo Kim, Michael B. Yaffe, Woolim Son, Namkyoung Kim, Tae-Ik Choi, Puspanjali Swain, Cheol-Hee Kim, Jin-Young Lee, Nathanael S. Gray, Kyung S. Lee, Taebo Sim
Summary: This study successfully designed and synthesized a series of macrocyclic peptidomimetics with high selectivity and inhibitory activities against Plk1's PBD. Compound 16e showed more potent inhibitory activity than the previous PMQSpTPL. The pi-π stacking interaction between 16a and Arg516 revealed a new design strategy, and PEGylation of 16h caused delocalization and mitotic failure of Plk1. Furthermore, the number of phospho-H3-positive cells in zebrafish embryos correlated with the amount of 16a. These findings suggest that macrocyclic peptidomimetics can serve as valuable templates for potent and novel Plk1-PBD inhibitors.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Oncology
Chuanyong Zhang, Chuangye Ni, Hao Lu
Summary: PLK2 plays an important role in the cell cycle, cell differentiation, and maintaining neural homeostasis. Dysfunction of PLK2 can lead to cell cycle disorders and developmental retardation. Additionally, PLK2 may promote cell survival or apoptosis in response to stress stimuli. However, research on the role of PLK2 in immunity to viral infection is limited compared to other family members.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Qamraa H. Al-Qahtani, Walid N. Moghrabi, Suhad Al-Yahya, Latifa Al-Haj, Maher Al-Saif, Linah Mahmoud, Falah Al-Mohanna, Norah Al-Souhibani, Ayodele Alaiya, Edward Hitti, Khalid S. A. Khabar
Summary: PLK1 inhibition reduces the expression and stability of ARE mRNAs in cancer cells by decreasing the phosphorylation level of ZFP36/TTP, a protein promoting mRNA decay.
MOLECULAR ONCOLOGY
(2021)
Review
Pharmacology & Pharmacy
Ilma Shakeel, Neha Basheer, Gulam Mustafa Hasan, Mohammad Afzal, Md. Imtaiyaz Hassan
Summary: PLK1, a conserved mitotic serine-threonine protein kinase, plays important roles in cell division and genome stability. Its expression is controlled by cell cycle stages and blocking PLK1 expression can inhibit tumor cell proliferation and induce apoptosis, making it an attractive target for drug development.
JOURNAL OF DRUG TARGETING
(2021)
Article
Immunology
Zhenqiang Gao, Cuiting Zheng, Yaqi Xing, Xiyu Zhang, Yunfei Bai, Chen Chen, Yuanyuan Zheng, Wen Wang, Hongbing Zhang, Yan Meng
Summary: In sepsis, Plk-1 promotes the development of SIMD. Inhibition of Plk-1 improves LPS-induced myocardial injury and inflammation, and enhances the survival rate of mice. Plk-1 inhibition also impedes NF-κB signal pathway activation.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Styliani Iliaki, Rudi Beyaert, Inna S. Afonina
Summary: PLK1 is a Ser/Thr kinase that plays crucial roles in cell cycle regulation, DNA damage response, apoptosis, and cancer progression. Overexpression of PLK1 is associated with poor prognosis in cancer, making it an attractive therapeutic target.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
Monica J. Bohmer, Jinhua Wang, Eva S. Istvan, Madeline R. Luth, Jennifer E. Collins, Edward L. Huttlin, Lushun Wang, Nimisha Mittal, Mingfeng Hao, Nicholas P. Kwiatkowski, Steven P. Gygi, Ratna Chakrabarti, Xianming Deng, Daniel E. Goldberg, Elizabeth A. Winzeler, Nathanael S. Gray, Debopam Chakrabarti
Summary: Protein kinases have been successful therapeutic targets, especially for cancer treatment, and there is potential to repurpose them as antimalarials. A study discovered BI-2536, a potent inhibitor of human polo-like kinase 1, showing nanomolar antiplasmodial activity. Screening of other PLK1 inhibitors identified more potential antimalarials, and a shared target, PfNEK3, was identified through kinase panel screening. However, there may be additional targets involved as distinct signaling pathways were disrupted by different inhibitors. Genomic analysis of BI-2536-resistant parasites suggested potential inhibition of an aminoacyl-tRNA synthetase.
ACS INFECTIOUS DISEASES
(2023)
Article
Respiratory System
Rongrong Chen, Hongfei Wang, Cuiting Zheng, Xiyu Zhang, Li Li, Shengwei Wang, Hongyu Chen, Jing Duan, Xian Zhou, Haiyong Peng, Jing Guo, Anchen Zhang, Feifei Li, Wang Wang, Yu Zhang, Jun Wang, Chen Wang, Yan Meng, Xinling Du, Hongbing Zhang
Summary: The study aimed to investigate the role of the mitotic regulator Polo-like kinase 1 (PLK1) in the development of pulmonary hypertension (PH). The results showed that hypoxia stimulated the expression of PLK1 through the induction of HIF1a and RELA. Overexpression of PLK1 was essential for the development of PH, suggesting that PLK1 could be a potential druggable target for PH.
RESPIRATORY RESEARCH
(2023)
Article
Biology
Liangyu Zhang, Weston T. Stauffer, John S. Wang, Fan Wu, Zhouliang Yu, Chenshu Liu, Hyung Jun Kim, Abby F. Dernburg
Summary: Meiotic chromosome segregation relies on synapsis and crossover recombination between homologous chromosomes. In C. elegans, recruitment of Polo-like kinase PLK-2 triggers phosphorylation and inactivation of CHK-2, an early meiotic kinase required for pairing, synapsis, and double-strand break induction. Inactivation of CHK-2 terminates double-strand break formation and enables crossover designation and cell cycle progression. These findings illuminate the mechanisms by which meiotic cells ensure crossover formation and accurate chromosome segregation.
Editorial Material
Cell Biology
John M. Ryniawec, Gregory C. Rogers
Summary: This article describes a new mechanism of Plk4 regulation, which restricts its translation through competitive ribosome binding at upstream open reading frames (uORFs) in mRNA. This mechanism is especially critical in the development of primordial germ cells in mice.
GENES & DEVELOPMENT
(2022)
Review
Biochemistry & Molecular Biology
Mrunal Jadhav, Kaksha Sankhe, Richie R. Bhandare, Zehra Edis, Samir Haj Bloukh, Tabassum Asif Khan
Summary: Recent decades have seen significant progress in the discovery of anticancer drugs containing pyrimidine structures, which exhibit diverse mechanisms of action, including inhibition of protein kinases. Literature and patent analysis reveal extensive research and application of pyrimidine derivatives in the field of anticancer drugs.
Article
Parasitology
Eun-Ah Park, Juri Kim, Mee Young Shin, Soon-Jung Park
Summary: The study reveals the role of GlPLK in Giardia cell division, especially during cytokinesis, and its involvement in flagella formation.
PARASITES & VECTORS
(2021)
Editorial Material
Biochemistry & Molecular Biology
Helge Paternoga, Daniel N. Wilson
Summary: Wang et al. (2022) use real-time single-molecule fluorescence spectroscopy to observe eukaryotic translation initiation events. They find that the engagement of mRNA by ribosomal 43S subunits is slow, but the subsequent mRNA scanning process is rapid, approximately 10 times faster than translation.
Article
Chemistry, Medicinal
Yin Sun, Yanli Xue, Pengkun Sun, Shuyi Mu, Hongbing Liu, Yu Sun, Lin Wang, Jingkai Wang, Tianxiao Wu, Wenbo Yin, Qiaohua Qin, Yixiang Sun, Nian Liu, Hanxun Wang, Huali Yang, Dongmei Zhao, Maosheng Cheng
Summary: A study discovered SP27 as the first selective PLK4 PROTAC degrader, which effectively degrades PLK4 and exhibits more potent inhibition of cell growth in TRIM37-amplified breast cancer. This finding is of great significance for the treatment of this cancer.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Chaofan Deng, Luyao Ren, Lin Yang, Xia Liu, Yanhui Dai, Jian Zhao, Tongtao Yue
Summary: This study investigates the interaction between black phosphorus (BP) nanomaterials with different degrees of degradation and centrosome polo-like kinase 1 (PLK1), a potential target for BP in inhibiting mitosis. The findings reveal the nonmonotonic relationship between BP degradation and its effectiveness in suppressing PLK1, providing new insights into the modulation of BP's bioactivity through degradation.
ENVIRONMENTAL SCIENCE-NANO
(2023)
