Article
Cell Biology
Manjuan Zhang, Fengrui Yang, Wenwen Wang, Najdat Zohbi, Xiwei Wang, Dongmei Wang, Xiaoxuan Zhuang, Zhen Dou, Dan Liu, Xiaoyu Song, Hadiyah-Nicole Green, Xing Liu, Xuebiao Yao
Summary: The dynamic interactions between SKAP and Aurora B via phase separation play a crucial role in orchestrating accurate interaction between the kinetochore and spindle microtubules during mitosis, ensuring faithful chromosome segregation and alignment. This novel mechanism forms a dynamic pool of Aurora B activity that facilitates the conversion of kinetochore-microtubule attachments from lateral to end-on, ultimately leading to successful cell division.
JOURNAL OF MOLECULAR CELL BIOLOGY
(2021)
Article
Plant Sciences
Jihee Hong, Dasom Gwon, Chang-Young Jang
Summary: Ginsenoside Rg1 reduces cancer cell proliferation by inhibiting Haspin kinase activity and H3T3ph, leading to decreased levels of Aurora B at the centromere.
JOURNAL OF GINSENG RESEARCH
(2022)
Article
Oncology
Justin A. Chen, Jasmine C. Huynh, Chun-Yi Wu, Ai-Ming Yu, Karen Matsukuma, Thomas J. Semrad, David R. Gandara, Tianhong Li, Jonathan W. Riess, Kit Tam, Philip C. Mack, Anthony Martinez, Nichole Mahaffey, Karen L. Kelly, Edward J. Kim
Summary: The combination therapy of alisertib and gemcitabine shows potential for disease control in heavily pre-treated tumors, but gastrointestinal and hematologic toxicity is apparent.
CANCER CHEMOTHERAPY AND PHARMACOLOGY
(2022)
Article
Oncology
Thomas J. Semrad, Edward J. Kim, I-Yeh Gong, Tianhong Li, Scott Christensen, Mili Arora, Jonathan W. Riess, David R. Gandara, Karen Kelly
Summary: This study aimed to evaluate the safety and tolerability of the Aurora A kinase inhibitor alisertib in combination with weekly irinotecan. The results showed that adult patients were unable to tolerate the combination treatment at clinically meaningful doses due to hematologic and gastrointestinal toxicities.
CANCER CHEMOTHERAPY AND PHARMACOLOGY
(2021)
Article
Medicine, Research & Experimental
Ziqi Yan, Qiong Shi, Xumei Liu, Jinghua Li, Vidula Ahire, Shenqiu Zhang, Jing Zhang, Dun Yang, Thaddeus D. Allen
Summary: Plants are a valuable source of bioactive compounds, and in this study, two phytochemicals, Corynoline and Acetylcorynoline, were found to have inhibitory effects on cancer cells by inducing mitotic arrest and polyploidy. The mechanism of action involves centrosome amplification and declustering, leading to the formation of multi-polar spindles. These compounds inhibited the viability of various human cancer cell lines and could be potential prototypes for the development of more potent and selective analogs in the future.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Immunology
Yu-Xiang Ma, Fu-Rong Liu, Yang Zhang, Qun Chen, Zhi-Qiang Chen, Qian-Wen Liu, Yan Huang, Yun-Peng Yang, Wen-Feng Fang, Ning Xi, Ning Kang, Yu-Lei Zhuang, Qi Zhang, Ying-Zhi Jiang, Li Zhang, Hong-Yun Zhao
Summary: CT053PTSA is a novel tyrosine kinase inhibitor that shows promising antitumor and antiangiogenic activity. The first-in-human study demonstrated that CT053PTSA is well tolerated and has a satisfactory safety profile. Further clinical trials are ongoing to evaluate the clinical activity of CT053PTSA.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Mandeep Singh, Lakshay Malhotra, Md Anzarul Haque, Mukesh Kumar, Alexander Tikhomirov, Valeria Litvinova, Alexander M. Korolev, A. S. Ethayathulla, Uddipan Das, Andrey E. Shchekotikhin, Punit Kaur
Summary: This study utilized a structure-based scaffold hopping approach to design a series of heteroarene-fused anthraquinone derivatives, which were then subjected to virtual screening and experimental evaluation to identify a compound that showed excellent in vitro inhibition of AurB.
Article
Cell Biology
M. Johansson, Y. Azuma, D. J. Clarke
Summary: DNA topoisomerase II (TopoII) plays a crucial role in mitosis by decatenating chromosomes. When the TopoII enzyme cycle stalls due to failed ATP hydrolysis, the onset of anaphase is delayed to ensure accurate chromosome segregation. Recent evidence shows that the TopoII checkpoint response requires Aurora B and Haspin kinases, and is triggered by SUMOylation of the C-terminal domain of TopoII.
Review
Chemistry, Physical
Priya, Shalini Jaswal, Ghanshyam Das Gupta, Sant Kumar Verma
Summary: Aurora kinase family plays a critical role in cell division and the cell cycle, and overexpression of AURKA and AURKB has been linked to the development of various carcinomas. The synthesis and development of Aurora Kinase inhibitors offer new opportunities for anticancer therapy.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Review
Chemistry, Medicinal
Tathagata Pradhan, Ojasvi Gupta, Gurpreet Singh, Vikramdeep Monga
Summary: Aurora kinases, a family of regulatory proteins playing a crucial role in cell proliferation, have emerged as validated drug targets for anticancer drug discovery. The design and development of Aurora kinase inhibitors have been widely explored as potential anticancer agents, showing promising results in growth inhibition and apoptosis in tumor cells.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Oncology
Elena Garralda, Alison M. Schram, Philippe L. Bedard, Gary K. Schwartz, Eunice Yuen, Samuel C. McNeely, Silvia Ribeiro, Jason Cunningham, Yi Wang, Arantxa Urunuela, Xiaojian Xu, Patricia LoRusso
Summary: LY3405105 is a promising CDK7 inhibitor with good bioavailability and selectivity. However, the clinical trial showed limited efficacy and no plans for further development. The MTD of LY3405105 monotherapy was determined to be 20 mg QD.
Article
Cell Biology
Eric M. C. Britigan, Jun Wan, Daniel K. Sam, Sarah E. Copeland, Amber L. Lasek, Laura C. F. Hrycyniak, Lei Wang, Anjon Audhya, Mark E. Burkard, Avtar Roopra, Beth A. Weaver
Summary: The increased expression of Aurora B protein reduces its kinase activity and causes defects in mitosis. The complexes of Aurora B and its binding partner INCENP achieve Aurora B activation through autophosphorylation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Oncology
Alessio Stefani, Geny Piro, Francesco Schietroma, Alessandro Strusi, Emanuele Vita, Simone Fiorani, Diletta Barone, Federico Monaca, Ileana Sparagna, Giustina Valente, Miriam Grazia Ferrara, Ettore D'Argento, Mariantonietta Di Salvatore, Carmine Carbone, Giampaolo Tortora, Emilio Bria
Summary: Lung cancer is categorized into NSCLC and SCLC, with the former having actionable targets for advanced treatment and the latter lacking oncogene-addiction concept. Aurora kinases (AURKs) play a crucial role in cell cycle progression and their overexpression is a common protumorigenic pathway in various cancer types, influencing drug resistance mechanisms.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Vijay H. Masand, Sami A. Al-Hussain, Mithilesh M. Rathore, Sumer D. Thakur, Siddhartha Akasapu, Abdul Samad, Aamal A. Al-Mutairi, Magdi E. A. Zaki
Summary: In this study, a comprehensive quantitative structure-activity relationship (QSAR) analysis was conducted using 561 structurally diverse aurora kinase B inhibitors. The resulting QSAR model showed high statistical performance and successfully identified key pharmacophoric features for inhibiting AKB.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Antal H. Kovacs, Dong Zhao, Jinqiang Hou
Summary: This paper presents a comprehensive review of the preclinical and clinical candidates of Aurora B inhibitors as potential anticancer drugs. The recent advances in the field of Aurora B inhibitor development will be highlighted, and the binding interactions between Aurora B and inhibitors based on crystal structures will be presented and discussed to provide insights for the future design of more selective Aurora B inhibitors.