606 results match your criteria plk1 inhibitor

Deciphering the performance of polo-like kinase 1 in triple-negative breast cancer progression according to the centromere protein U-phosphorylation pathway.

Am J Cancer Res 2021 15;11(5):2142-2158. Epub 2021 May 15.

The 3rd Department of Breast Cancer, Treatment and Research Center, China Tianjin Breast Cancer Prevention, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer Huan Hu Xi Road, Ti Yuan Bei, He Xi District, Tianjin 300060, People's Republic of China.

In general, the lack of effective therapeutic targets has led to the poor prognosis of triple-negative breast cancer (TNBC). Polo-like kinase 1 (PLK1) has been studied extensively as an effective therapeutic objective for the progression of tumor. Although the fundamental strategy and function of PLK1 in TNBC are still unclear. Read More

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Glucocappasalin Induces G2/M-Phase Arrest, Apoptosis, and Autophagy Pathways by Targeting CDK1 and PLK1 in Cervical Carcinoma Cells.

Front Pharmacol 2021 20;12:671138. Epub 2021 May 20.

Clinical Genetics Laboratory, Clinical Medical College, Affiliated Hospital and College of Basic Medicine and School of Pharmacy and School of Food and Biological Engineering, Chengdu University, Chengdu, China.

Glucocappasalin (GCP), a natural product derived from the seeds of (L.) Webb. ex Prantl, exhibits potential antitumor activity in HeLa cervical carcinoma cells. Read More

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Co-Targeting Plk1 and DNMT3a in Advanced Prostate Cancer.

Adv Sci (Weinh) 2021 May 29:e2101458. Epub 2021 May 29.

Department of Biomedical Informatics, The Ohio State University, Columbus, OH, 43210, USA.

Because there is no effective treatment for late-stage prostate cancer (PCa) at this moment, identifying novel targets for therapy of advanced PCa is urgently needed. A new network-based systems biology approach, XDeath, is developed to detect crosstalk of signaling pathways associated with PCa progression. This unique integrated network merges gene causal regulation networks and protein-protein interactions to identify novel co-targets for PCa treatment. Read More

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Protein synthesis inhibitor omacetaxine is effective against hepatocellular carcinoma.

JCI Insight 2021 May 18. Epub 2021 May 18.

Department of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, United States of America.

Hepatocellular carcinoma (HCC) is the 6th-most common and the 4th-most deadly cancer worldwide. The development cost of new therapeutics is a major limitation in patient outcomes. Importantly, there is a paucity of preclinical HCC models in which to test new small molecules. Read More

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Hyperactivation of HER2-SHCBP1-PLK1 axis promotes tumor cell mitosis and impairs trastuzumab sensitivity to gastric cancer.

Nat Commun 2021 05 14;12(1):2812. Epub 2021 May 14.

Cuiying Biomedical Research Center, Lanzhou University Second Hospital, Lanzhou, People's Republic of China.

Trastuzumab is the backbone of HER2-directed gastric cancer therapy, but poor patient response due to insufficient cell sensitivity and drug resistance remains a clinical challenge. Here, we report that HER2 is involved in cell mitotic promotion for tumorigenesis by hyperactivating a crucial HER2-SHCBP1-PLK1 axis that drives trastuzumab sensitivity and is targeted therapeutically. SHCBP1 is an Shc1-binding protein but is detached from scaffold protein Shc1 following HER2 activation. Read More

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Design and Synthesis of a Novel PLK1 Inhibitor Scaffold Using a Hybridized 3D-QSAR Model.

Int J Mol Sci 2021 Apr 8;22(8). Epub 2021 Apr 8.

College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan 426-791, Korea.

Polo-like kinase 1 (PLK1) plays an important role in cell cycle progression and proliferation in cancer cells. PLK1 also contributes to anticancer drug resistance and is a valuable target in anticancer therapeutics. To identify additional effective PLK1 inhibitors, we performed QSAR studies of two series of known PLK1 inhibitors and proposed a new structure based on a hybridized 3D-QSAR model. Read More

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A survey of the kinome pharmacopeia reveals multiple scaffolds and targets for the development of novel anthelmintics.

Sci Rep 2021 Apr 28;11(1):9161. Epub 2021 Apr 28.

Department of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A8, Canada.

Over one billion people are currently infected with a parasitic nematode. Symptoms can include anemia, malnutrition, developmental delay, and in severe cases, death. Resistance is emerging to the anthelmintics currently used to treat nematode infection, prompting the need to develop new anthelmintics. Read More

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High and synergistic activity between mTORC1 and PLK1 inhibition in adenocarcinoma NSCLC.

Oncotarget 2021 Apr 13;12(8):859-872. Epub 2021 Apr 13.

Laboratory of Preclinical Investigation, Department of Translational Research, Institut Curie, PSL University, Paris, France.

Significant rational is available for specific targeting of PI3K/AKT/mTOR pathway in the treatment of non-small cell lung cancer (NSCLC). However, almost all clinical trials that have evaluated Pi3K pathway-based monotherapies/combinations did not observe an improvement of patient's outcome. The aim of our study was therefore to define combination of treatment based on the determination of predictive markers of resistance to the mTORC1 inhibitor RAD001/Everolimus. Read More

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Differential Expression of Potential Biomarkers of Oral Squamous Cell Carcinoma Development.

Head Neck Pathol 2021 Apr 11. Epub 2021 Apr 11.

Departamento de Patologia, Programa de Pós-Graduação Em Biotecnologia, Centro de Ciências da Saúde - Universidade Federal do Espírito santo, Av. Marechal Campos, 1468 Maruípe, Vitoria, Espírito Santo, 29.043-900, Brazil.

To evaluate molecular epithelial changes, we investigated whether a profile of survivin, cyclin dependent kinase inhibitor 2A (CDKN2A), epidermal growth factor receptor (EGFR), polo like kinase 1 (PLK1), p63, p40 (Δnp63 isoform), cyclin D1 (CCND1) and BCL2 apoptosis regulator (BCL2) proteins could predict malignant transformation. Different tissue segments (tumor adjacent epithelium; dysplasia and tumor) from a total of 109 patients were analyzed by immunohistochemistry. An increased expression of survivin (p < 0. Read More

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7-(2-Anilinopyrimidin-4-yl)-1-benzazepin-2-ones Designed by a "Cut and Glue" Strategy Are Dual Aurora A/VEGF-R Kinase Inhibitors.

Molecules 2021 Mar 14;26(6). Epub 2021 Mar 14.

Institut für Medizinische und Pharmazeutische Chemie, Technische Universität Braunschweig, Beethovenstraße 55, 38106 Braunschweig, Germany.

Although overexpression and hyperactivity of protein kinases are causative for a wide range of human cancers, protein kinase inhibitors currently approved as cancer drugs address only a limited number of these enzymes. To identify new chemotypes addressing alternative protein kinases, the basic structure of a known PLK1/VEGF-R2 inhibitor class was formally dissected and reassembled. The resulting 7-(2-anilinopyrimidin-4-yl)-1-benzazepin-2-ones were synthesized and proved to be dual inhibitors of Aurora A kinase and VEGF receptor kinases. Read More

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Synergistic Therapy for Cervical Cancer by Codelivery of Cisplatin and JQ1 Inhibiting Plk1-Mutant Trp53 Axis.

Nano Lett 2021 03 11;21(6):2412-2421. Epub 2021 Mar 11.

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.

JQ1, a specific inhibitor of bromodomain-containing protein 4 (BRD4), could have great potential in the treatment of cervical cancer. However, its clinical application is limited by its short plasma half-life and limited antitumor efficacy. In this work, cisplatin (CDDP) was first utilized as the stabilizer and cooperator in the nanosystem (mPEG--P(Glu--Phe)-CDDP/JQ1, called PGP-CDDP/JQ1) to break through the efficiency limitation of JQ1. Read More

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CRISPR-Mediated Kinome Editing Prioritizes a Synergistic Combination Therapy for -Amplified Lung Cancer.

Cancer Res 2021 Jun 8;81(11):3121-3133. Epub 2021 Mar 8.

Division of General Thoracic Surgery, Inselspital, Bern University Hospital, University of Bern, Switzerland.

Oncogenic activation of the FGFR pathway is frequent in lung and other cancers. However, due to drug resistance, pharmacological blockage of aberrant FGFR signaling has provided little clinical benefit in patients with -amplified tumors. The determining factors for the limited efficacy of FGFR-targeted therapy remain incompletely understood. Read More

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Design, synthesis, and biological evaluation of novel 4,4-difluoro-1-methyl-N, 6-diphenyl-5, 6-dihydro-4H-pyrimido [4, 5-b] [1, 2, 4] triazolo [4, 3-d] [1, 4] diazepin-8-amine derivatives as potential BRD4 inhibitors.

Chem Biol Drug Des 2021 May 6;97(5):1117-1128. Epub 2021 Mar 6.

Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.

Bromodomain-containing protein 4 (BRD4) plays an extremely important physiological role in cancer, and the BRD4 inhibitors can effectively inhibit the proliferation of tumor cells. By taking BI-2536 (PLK1 and BRD4 inhibitor) as the lead compound, sixteen novel BRD4 inhibitors with the 4,4-difluoro-1-methyl-N,6-diphenyl-5,6-dihydro-4H-pyrimido[4,5-b] [1,2,4] triazolo[4,3-d] [1,4] diazepine-8-amine structure were designed and synthetized. Among the target compounds, compound 15h exhibited outstanding inhibition for BRD4-BD1 (IC value of 0. Read More

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Efficient biosynthesis of (S)-1-[2-(trifluoromethyl)phenyl]ethanol by a novel isolate Geotrichum silvicola ZJPH1811 in deep eutectic solvent/cyclodextrin-containing system.

Bioresour Technol 2021 Jun 12;329:124832. Epub 2021 Feb 12.

Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, People's Republic of China. Electronic address:

This study aimed to develop a biotransformation process for the production of (S)-1-[2-(trifluoromethyl)phenyl]ethanol, a key chiral intermediate of Plk1 inhibitor, and increase its productivity through medium engineering strategy. A fungus isolate Geotrichum silvicola ZJPH1811 was adopted as biocatalyst for 2'-(trifluoromethyl)acetophenone reduction, and gave the best performance with > 99.2% product ee. Read More

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PLK1 Inhibition Sensitizes Breast Cancer Cells to Radiation via Suppressing Autophagy.

Int J Radiat Oncol Biol Phys 2021 Feb 20. Epub 2021 Feb 20.

Department of Radiation Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, Guangdong Province, People's Republic of China. Electronic address:

Purpose: Polo-like kinase 1 (PLK1) is a protein kinase that is overexpressed in breast cancer and may represent an attractive target for breast cancer treatment. However, few studies have investigated the relationship between PLK1 and radiosensitivity in breast cancer. Here, we attempted to explore whether PLK1 inhibition could sensitize breast cancer cells to radiation. Read More

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February 2021

Dual Inhibition of γ-Tubulin and Plk1 Induces Mitotic Cell Death.

Front Pharmacol 2020 29;11:620185. Epub 2021 Jan 29.

Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Japan.

α/β-Tubulin inhibitors that alter microtubule (MT) dynamics are commonly used in cancer therapy, however, these inhibitors also cause severe side effects such as peripheral neuropathy. γ-Tubulin is a possible target as antitumor drugs with low side effects, but the antitumor effect of γ-tubulin inhibitors has not been reported yet. In this study, we verified the antitumor activity of gatastatin, a γ-tubulin specific inhibitor. Read More

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January 2021

α integrin-binding peptide-functionalized polymersomes loaded with volasertib for dually-targeted molecular therapy for ovarian cancer.

Acta Biomater 2021 04 6;124:348-357. Epub 2021 Feb 6.

Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, and State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, 215123, PR China. Electronic address:

Ovarian cancer (OC) is a high-mortality malignancy in women with a five-year survival rate of 30-40%. There is an urgent need to develop high-efficacy and low toxic treatments for OC. Herein, we report an appealing strategy that combines α integrin targeted polymersomes (A3-Ps) and targeted molecular drug, polo-like kinase 1 (PLK1) inhibitor volasertib (Vol) for dually targeted molecular therapy of OC in vivo. Read More

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Elucidation of Novel Therapeutic Targets for Breast Cancer with Fusion.

J Clin Med 2021 Feb 4;10(4). Epub 2021 Feb 4.

Precision Medicine Center, Seoul National University Bundang Hospital, Seongnam 13620, Korea.

Among the various types of breast cancer, the luminal B subtype is the most common in young women, and (E:C) fusion is the most frequent oncogenic fusion driver of the luminal B subtype. Nevertheless, treatments targeting E:C fusion has not been well established yet. Hence, the aim of this study is to investigate potential therapies targeting E:C fusion based on systematic bioinformatical analysis of the Cancer Genome Atlas (TCGA) data. Read More

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February 2021

The tyrosine kinase v-Src modifies cytotoxicities of anticancer drugs targeting cell division.

J Cell Mol Med 2021 Feb 19;25(3):1677-1687. Epub 2021 Jan 19.

Department of Biochemistry and Molecular Biology, Kyoto Pharmaceutical University, Kyoto, Japan.

v-Src oncogene causes cell transformation through its strong tyrosine kinase activity. We have revealed that v-Src-mediated cell transformation occurs at a low frequency and it is attributed to mitotic abnormalities-mediated chromosome instability. v-Src directly phosphorylates Tyr-15 of cyclin-dependent kinase 1 (CDK1), thereby causing mitotic slippage and reduction in Eg5 inhibitor cytotoxicity. Read More

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February 2021

Corrigendum to "A PLK1 kinase inhibitor enhances the chemosensitivity of cisplatin by inducing pyroptosis in oesophageal squamous cell carcinoma" [EBioMedicine 41 (2019) 244-255].

EBioMedicine 2021 Jan 6;63:103041. Epub 2021 Jan 6.

Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China. Electronic address:

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January 2021

Kinome inhibition reveals a role for polo-like kinase 1 in targeting post-transcriptional control in cancer.

Mol Oncol 2021 Jan 7. Epub 2021 Jan 7.

Molecular BioMedicine Program, Faisal Specialist Hospital and Research Centre, Riyadh, King, Saudi Arabia.

Dysfunctions in post-transcriptional control are observed in cancer and chronic inflammatory diseases. Here, we employed a kinome inhibitor library (n = 378) in a reporter system selective for 3'-untranslated region-AU-rich elements (ARE). Fifteen inhibitors reduced the ARE-reporter activity; among the targets is the polo-like kinase 1 (PLK1). Read More

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January 2021

Targeting Kinases in : Anthelminthic Effects and Tissue Distribution of Selected Kinase Inhibitors.

Front Vet Sci 2020 21;7:611270. Epub 2020 Dec 21.

Biomedical Research Center Seltersberg (BFS), Institute of Parasitology, Justus Liebig University Giessen, Giessen, Germany.

Protein kinases have been discussed as promising druggable targets in various parasitic helminths. New drugs are also needed for control of fascioliasis, a food-borne trematode infection and worldwide spread zoonosis, caused by the liver fluke and related species. In this study, we intended to move protein kinases more into the spotlight of drug research and characterized the fasciolicidal activity of two small-molecule inhibitors from human cancer research: the Abelson tyrosine kinase (ABL-TK) inhibitor imatinib and the polo-like 1 (PLK1) inhibitor BI2536. Read More

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December 2020

Polo like kinase 1 expression in cervical cancer tissues generated from multiple detection methods.

PeerJ 2020 8;8:e10458. Epub 2020 Dec 8.

Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China.

Background: Existing studies of PLK1 in cervical cancer had several flaws. The methods adopted by those studies of detecting PLK1 expression in cervical cancer were single and there lacks comprehensive evaluation of the clinico-pathological significance of PLK1 in cervical cancer.

Methods: A total of 303 cervical tissue samples were collected for in-house tissue microarrays. Read More

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December 2020

PLK1 (polo like kinase 1)-dependent autophagy facilitates gefitinib-induced hepatotoxicity by degrading COX6A1 (cytochrome c oxidase subunit 6A1).

Autophagy 2020 Dec 14:1-17. Epub 2020 Dec 14.

Institute of Pharmacology & Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.

Liver dysfunction is an outstanding dose-limiting toxicity of gefitinib, an EGFR (epidermal growth factor receptor)-tyrosine kinase inhibitor (TKI), in the treatment of EGFR mutation-positive non-small cell lung cancer (NSCLC). We aimed to elucidate the mechanisms underlying gefitinib-induced hepatotoxicity, and provide potentially effective intervention strategy. We discovered that gefitinib could sequentially activate macroautophagy/autophagy and apoptosis in hepatocytes. Read More

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December 2020

[Mining Polo-Box domain of Polo-like kinase 1 as a new therapeutic target for cancer].

Sheng Wu Gong Cheng Xue Bao 2020 Nov;36(11):2298-2312

Institute for Drug Screening and Evaluation, Wannan Medical College, Wuhu 241002, Anhui, China.

Polo-like kinase 1 (Plk1) is widely regarded as one of the most promising targets for cancer therapy due to its essential role in cell division and tumor cell survival. At present, most Plk1 inhibitors have been developed based on kinase domain, some of which are in clinical trial. However, inhibitors targeting kinase domain face off-target effect and drug resistance owing to the conserved nature and the frequent mutations in the ATP-binding pocket. Read More

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November 2020

Calibrated liposomal release of the anti-mitotic agent BI-2536 increases the targeting of mitotic tumor cells.

Eur J Pharm Biopharm 2020 Dec 22;157:183-190. Epub 2020 Oct 22.

Temasek Life Sciences Laboratory, Singapore; Department of Biological Sciences, National University of Singapore, Singapore. Electronic address:

Cancer drugs which are specifically targeted at mitosis have generally under-delivered as a class. One likely reason is that only a small percentage of cancer cells in a tumor are actually dividing at any moment. If this is the case, then prolonged bioavailability in the tumor should significantly increase the efficacy of antimitotic agents. Read More

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December 2020

Combination of Inhibitors of USP7 and PLK1 has a Strong Synergism against Paclitaxel Resistance.

Int J Mol Sci 2020 Nov 16;21(22). Epub 2020 Nov 16.

Department of Pharmacy, College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Gyeonggi-do 15588, Korea.

USP7 is a promising target for the development of cancer treatments because of its high expression and the critical functions of its substrates in carcinogenesis of several different carcinomas. Here, we demonstrated the effectiveness of targeting USP7 in advanced malignant cells showing high levels of USP7, especially in taxane-resistant cancer. USP7 knockdown effectively induced cell death in several cancer cells of lung, prostate, and cervix. Read More

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November 2020

Non-mitotic functions of polo-like kinases in cancer cells.

Biochim Biophys Acta Rev Cancer 2021 01 7;1875(1):188467. Epub 2020 Nov 7.

Department of Gynecology, Goethe-University, Frankfurt, Germany; German Cancer Consortium (DKTK), German Cancer Research Center, Partner Site Frankfurt am Main, Frankfurt, Germany. Electronic address:

Inhibitors of mitotic protein kinases are currently being developed as non-neurotoxic alternatives of microtubule-targeting agents (taxanes, vinca alkaloids) which provide a substantial survival benefit for patients afflicted with different types of solid tumors. Among the mitotic kinases, the cyclin-dependent kinases, the Aurora kinases, the kinesin spindle protein and Polo-like kinases (PLKs) have emerged as attractive targets of cancer therapeutics. The functions of mammalian PLK1-5 are traditionally linked to the regulation of the cell cycle and to the stress response. Read More

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January 2021

Small-molecule inhibitors of breast cancer-related targets: Potential therapeutic agents for breast cancer.

Eur J Med Chem 2021 Jan 29;210:112954. Epub 2020 Oct 29.

Department of Medicinal Chemistry, School of Pharmacy, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, Shandong, 271016, PR China.

Despite dramatic advances in cancer research and therapy, breast cancer remains a tricky health problem and represents a top biomedical research priority. Nowadays, breast cancer is still the leading cause of malignancy-related deaths in women, and incidence and mortality rates of it are expected to increase significantly the next years. Currently more and more researchers are interested in the study of breast cancer by its arising in young women. Read More

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January 2021

Development of a Polo-like Kinase-1 Polo-Box Domain Inhibitor as a Tumor Growth Suppressor in Mice Models.

J Med Chem 2020 12 3;63(23):14905-14920. Epub 2020 Nov 3.

Division of Magnetic Resonance, Korea Basic Science Institute (KBSI), Ochang, Chung Buk 28119, Republic of Korea.

Polo-like kinase-1 (Plk1) plays a key role in mitosis and has been identified as an attractive anticancer drug target. Plk1 consists of two drug-targeting sites, namely, N-terminal kinase domain (KD) and C-terminal polo-box domain (PBD). As KD-targeting inhibitors are associated with severe side effects, here we report on the pyrazole-based Plk1 PBD inhibitor, KBJK557, which showed a remarkable anticancer effect by inducing Plk1 delocalization, mitotic arrest, and apoptosis in HeLa cells. Read More

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December 2020