Identification of novel polo-like kinase 1 inhibitors by a hybrid virtual screening

Chemical Biology & Drug Design
Shuai LuTao Lu

Abstract

Polo-like kinase 1 is an important and attractive oncological target that plays a key role in mitosis and cytokinesis. A combined pharmacophore- and docking-based virtual screening was performed to identify novel polo-like kinase 1 inhibitors. A total of 34 hit compounds were selected and tested in vitro, and some compounds showed inhibition of polo-like kinase 1 and human tumor cell growth. The most potent compound (66) inhibited polo-like kinase 1 with an IC(50) value of 6.99 μm. The docked binding models of two hit compounds were discussed in detail. These compounds contained novel chemical scaffolds and may be used as foundations for the development of novel classes of polo-like kinase 1 inhibitors.

References

Jun 25, 1998·Molecular and Cellular Biology·Y W QianJ L Maller
Sep 6, 2002·Oncogene·Wei DaiFrank Traganos
May 19, 2004·Proceedings of the National Academy of Sciences of the United States of America·Yakir MosheAvram Hershko
Jan 11, 2005·Oncogene·Drew M LoweryMichael B Yaffe
Jan 11, 2005·Oncogene·Noriyuki TakaiIsao Miyakawa
Apr 28, 2005·Current Topics in Medicinal Chemistry·Campbell McInnesPeter M Fischer
Jan 20, 2006·Journal of Medicinal Chemistry·Woody ShermanRamy Farid
Mar 25, 2006·Nature Reviews. Cancer·Klaus Strebhardt, Axel Ullrich
Jun 24, 2006·Drug Discovery Today·Gerhard Klebe
Oct 10, 2006·Nature Chemical Biology·Ulf PetersTarun M Kapoor
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Mark E BurkardPrasad V Jallepalli
Apr 28, 2007·Biochemistry·Michael KotheYuan-Hua Ding
Nov 17, 2007·Chemical Biology & Drug Design·Michael KotheYuan-Hua Ding
Mar 18, 2008·Drug Discovery Today·Bohdan Waszkowycz
Mar 19, 2008·Bioorganic & Medicinal Chemistry Letters·Tian ZhuTao Lu
Aug 12, 2008·Mini Reviews in Medicinal Chemistry·Ingo Muegge
Oct 25, 2008·European Journal of Medicinal Chemistry·Hui-Fang LiYa-Dong Chen
Jan 13, 2009·European Journal of Medicinal Chemistry·Yadong ChenQidong You
Jan 21, 2009·Chemical Biology & Drug Design·Hui-Yuan WangSheng-Yong Yang
Apr 11, 2009·Journal of Medicinal Chemistry·Yunxiang LuWeiliang Zhu
Jul 11, 2009·Bioorganic & Medicinal Chemistry Letters·Yoshiyuki SatoYoshikazu Iwasawa
Dec 17, 2009·Journal of Medicinal Chemistry·Fabio ZuccottoMauro Angiolini
Jan 14, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yan Degenhardt, Thomas Lampkin
Mar 26, 2010·Journal of Medicinal Chemistry·Valeria OnnisDavid G Lloyd
Apr 2, 2010·Nature Reviews. Drug Discovery·Gisbert Schneider
Jun 12, 2010·Bioorganic & Medicinal Chemistry·Kristoff T HomanCynthia V Stauffacher
Jul 24, 2010·Bioorganic & Medicinal Chemistry Letters·Werner J GeldenhuysRichard T Carroll
Jul 31, 2010·Nature Reviews. Drug Discovery·Klaus Strebhardt
Oct 12, 2010·Bioorganic & Medicinal Chemistry Letters·Italo BeriaMichele Caruso
Jan 20, 2011·Molecular and Cellular Biology·Guillermo de CárcerMarcos Malumbres
Mar 29, 2011·Journal of Chemical Information and Modeling·Haoliang YuanYadong Chen
Apr 8, 2011·Bioorganic & Medicinal Chemistry Letters·Italo BeriaBarbara Valsasina
Apr 28, 2011·Journal of Molecular Modeling·Ting RanYadong Chen
May 24, 2011·Drug Discovery Today·Campbell McInnes, Michael D Wyatt

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.