Antibiotics switch to anticancer target

Author(s):  
Katie Kingwell
Keyword(s):  
2020 ◽  
Vol 17 (2) ◽  
Author(s):  
Sun‐Young Yoon ◽  
Do‐Hwi Kim ◽  
Kyung Min Roh ◽  
Dohee Ahn ◽  
Hyo Jin Kang ◽  
...  
Keyword(s):  

2021 ◽  
Author(s):  
Lun Zhang ◽  
Chenxi Cao ◽  
Jia Jin ◽  
Yaohua Fan ◽  
Xiaoguang Wang ◽  
...  

Abstract Protein arginine methyltransferase 5 (PRMT5), an important member in PRMT family, has been validated as a promising anticancer target. In this study, through the combination of virtual screening and biological experiments, we have identified two PRMT5 inhibitors with novel scaffold structures. Among them, compound Y2431 showed moderate activity with IC50 value of 10.09 μM and displayed good selectivity against other methyltransferases. The molecular docking analysis and molecular dynamics (MD) simulations suggested that the compound occupied the substrate-arginine binding site. Furthermore, Y2431 exhibited anti-proliferative activity to leukemia cells by inducing cell cycle arrest. Overall, the hit compound could provide a novel scaffold for further optimization of small-molecule PRMT5 inhibitors.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Mauro Salvi ◽  
Christian Borgo ◽  
Lorenzo A. Pinna ◽  
Maria Ruzzene

AbstractCK2 is a protein kinase involved in several human diseases (ranging from neurological and cardiovascular diseases to autoimmune disorders, diabetes, and infections, including COVID-19), but its best-known implications are in cancer, where it is considered a pharmacological target. Several CK2 inhibitors are available and clinical trials are underway in different cancer types. Recently, the suitability of CK2 as a broad anticancer target has been questioned by the finding that a newly developed compound, named SGC-CK2-1, which is more selective than any other known CK2 inhibitor, is poorly effective in reducing cell growth in different cancer lines, prompting the conclusion that the anticancer efficacy of CX-4945, the commonly used clinical-grade CK2 inhibitor, is to be attributed to its off-target effects. Here we perform a detailed scrutiny of published studies on CK2 targeting and a more in-depth analysis of the available data on SGC-CK2-1 vs. CX-4945 efficacy, providing a different perspective about the actual reliance of cancer cells on CK2. Collectively taken, our arguments would indicate that the pretended dispensability of CK2 in cancer is far from having been proved and warn against premature conclusions, which could discourage ongoing investigations on a potentially valuable drug target.


Molecules ◽  
2019 ◽  
Vol 24 (23) ◽  
pp. 4351 ◽  
Author(s):  
Yunjiang Zhou ◽  
Fang Yan ◽  
Xiangyun Huo ◽  
Miao-Miao Niu

Polo-box domain of polo-like kinase 1 (PLK1-PBD) has a pivotal role in cell proliferation and could be implicated as a potential anticancer target. Although some small-molecule inhibitors have been developed, their clinical application has been restricted by the poor selectivity. Therefore, there is an urgent need to develop effective PLK1-PBD inhibitors. Herein, we have developed a virtual screening protocol to find PLK1-PBD inhibitors by using combination of structure-based pharmacophore modeling and molecular docking. This protocol was successfully applied to screen PLK1-PBD inhibitors from specs database. MTT assay indicated that five screened hits suppressed the growth of HeLa cells. Particularly, hit-5, as a selective PLK1 inhibitor targeting PLK1-PBD, significantly inhibited the progression of HeLa cells-derived xenograft, with no obvious side effects. This work demonstrates that hit-5 may be a potential anticancer agent.


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