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polo-like kinase 4 (plk4; stk18)

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THE DISTILLERY SciBX: Science–Business eXchange Copyright © 2013 Nature Publishing Group 1 This week in therapeutics Indication Target/marker/ pathway Summary Licensing status Publication and contact information Cancer Breast cancer Polo-like kinase 4 (PLK4; STK18) In vitro and mouse studies identified small molecule PLK4 inhibitors that could help treat breast cancer. Computational modeling, chemical synthesis and in vitro testing of (indazolyl)methylene indolinone analogs identified several lead compounds as selective, nanomolar inhibitors of PLK4. In multiple human breast cancer cell lines, one lead compound inhibited growth at low nanomolar IC 50 values. In mice with xenograſt breast tumors, the lead compound decreased tumor growth compared with vehicle. Ongoing work includes IND-enabling studies of an optimized PLK4 inhibitor and planning of a Phase I trial of that inhibitor to treat solid tumors. SciBX 6(31); doi:10.1038/scibx.2013.819 Published online Aug. 15, 2013 Patented by the University Health Network; available for licensing or partnering Laufer, R. et al. J. Med. Chem.; published online July 6, 2013; doi:10.1021/jm400380m Contact: Henry W. Pauls, e Campbell Family Cancer Research Institute at the Princess Margaret Cancer Centre, Toronto, Ontario, Canada e-mail: [email protected]

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Page 1: Polo-like kinase 4 (PLK4; STK18)

the distillery

SciBX: Science–Business eXchange Copyright © 2013 Nature Publishing Group 1

This week in therapeutics

IndicationTarget/marker/pathway Summary Licensing status

Publication and contact information

Cancer

Breast cancer Polo-like kinase 4 (PLK4; STK18)

In vitro and mouse studies identified small molecule PLK4 inhibitors that could help treat breast cancer. Computational modeling, chemical synthesis and in vitro testing of (indazolyl)methylene indolinone analogs identified several lead compounds as selective, nanomolar inhibitors of PLK4. In multiple human breast cancer cell lines, one lead compound inhibited growth at low nanomolar IC50 values. In mice with xenograft breast tumors, the lead compound decreased tumor growth compared with vehicle. Ongoing work includes IND-enabling studies of an optimized PLK4 inhibitor and planning of a Phase I trial of that inhibitor to treat solid tumors.

SciBX 6(31); doi:10.1038/scibx.2013.819 Published online Aug. 15, 2013

Patented by the University Health Network; available for licensing or partnering

Laufer, R. et al. J. Med. Chem.; published online July 6, 2013; doi:10.1021/jm400380m Contact: Henry W. Pauls, The Campbell Family Cancer Research Institute at the Princess Margaret Cancer Centre, Toronto, Ontario, Canada e-mail: [email protected]

http://www.biocentury.com/targets/polo-like_kinase_4?utm_source=nature
http://www.biocentury.com/targets/plk4?utm_source=nature
http://www.biocentury.com/targets/stk18?utm_source=nature
http://www.uhn.ca/
http://www.uhn.ca/
mailto:[email protected]

Polo-like kinase 1 coordinates biosynthesis during cell

Research Paper Expression of Polo-Like Kinase … Polo-like kinase 4(PLK4) is an evolutionarily regulator involved in important ... citrate buffer (pH 6.0). After serial blocking with

Polo-like kinase 4 transcription is activated via CRE and NRF1

Plk4 and Aurora A cooperate in the initiation of

University of Groningen Inflammation and remodelling in ...TGF-β-activated kinase 1 (TAK1), a serine/threonine kinase, is a member of the mitogen activated protein kinase kinase kinase

Role for polo-like kinase 4 in mediation of cytokinesisas in tumor progression and aggressiveness (13). PLK4 is found on human chromosome 4q28, a region that frequently undergoes loss

The molecular docking of 1,4-naphthoquinone …The molecular docking of 1,4-naphthoquinone derivatives as inhibitors of Polo-like kinase 1 using Molegro Virtual Docker Susi Kusumaningrum

Oncogenic Regulators and Substrates of the Anaphase ...med.stanford.edu/labs/vanderijn-west/documents/1793.pdfand polo-like kinase 1, the anaphase promoting com-plex/cyclosome

Binding of STIL to Plk4 activates kinase activity to promote ......of the parental centriole and transitions at the beginning of S phase to an asymmetric spot on the parental centriole

Volasertib (BI 6727), a novel polo-like kinase inhibitor, reverses

Binding of STIL to Plk4 activates kinase activity to ... Cell... · STIL activates Plk4 by promoting self-phosphorylation of the activation loop of the kinase. ... cells led to the

Volasertib (BI 6727), a novel polo-like kinase inhibitor

POLO POLO

Molecular and structural basis of polo-like kinase 1 ...€¦ · Molecular and structural basis of polo-like kinase 1 substrate recognition: Implications in centrosomal localization

Mammalian Polo-like Kinase 1-dependent Regulation of the PBIP1

Mechanism of action Kinase inhibitor Tyrosine kinase inhibitor Proteasome inhibitor Kinase inhibitor, targets HER2 Immunomodulatory drug Kinase inhibitor Non-steroidal aromatase

Kinase-Glo Luminescent Kinase Assay Platform · The Kinase-Glo® Luminescent Kinase Assay Platform provides a homogeneous, high-throughput screening method for measuring kinase activity

Putting a bit into the polo-box domain of polo-like kinase 1 · REVIEW Open Access Putting a bit into the polo-box domain of polo-like kinase 1 Jung-Eun Park1, Tae-Sung Kim1, Lingjun

Research Article Use of the Polo-like kinase 4 (PLK4) inhibitor … · 2020. 8. 27. · Research Article Use of the Polo-like kinase 4 (PLK4) inhibitor centrinone to investigate intracellular

Autoinhibition and relief mechanism for Polo-like kinase 4Autoinhibition and relief mechanism for Polo-like kinase 4 Joseph E. Klebbaa, Daniel W. Bustera, Tiffany A. McLamarraha, Nasser

Volasertib (BI 6727), a novel polo-like kinase inhibitor ... · The IC50 values of each agent ... was assessed using CompuSyn (CompuSyn Inc., Paramus, NJ), ... To determine significant

University of Groningen Polo-Like Kinase-1 Controls Aurora A … · 2018-02-11 · Polo-Like Kinase-1 Controls Aurora A Destruction by Activating APC/C-Cdh1 Renske van Leuken1, Linda

CELL BIOLOGY Reversible centriole depletionwith an inhibitor of … · cancer cells, we developed centrinone, a reversible inhibitor of Polo-like kinase 4 (Plk4), a serine-threonine

Research Article High Expression of Polo-Like Kinase 1 Is

Binding of STIL to Plk4 activates kinase activity to promote centriole

Evaluation of Polo‐like kinase 1 as a potential … of Polo-like kinase 1 as a potential therapeutic target in Merkel cell carcinoma ... to assess the expression of Polo-like

Polo-like kinase 4 inhibition produces polyploidy and ... · cell death after chromosome missegregation and mitotic defects (26, 27). Indeed, depletion of PLK4 by RNAi hinders centriole

Polo-like kinase (PLK) inhibitor, Ro5203280, has potent ... · #These two authors, AKL Cheung and JCY Ip, contributed equally to this manuscript. Running Title: PLK inhibitor with

Schistosoma mansoni polo-like kinase 1 (SmPLK1) as a ...RNA interference (RNAi) of the Schistosoma mansoni ortholog of human polo-like kinase (PLK)1 elicits marked deleterious phenotypic

Original Article Volasertib suppresses the growth of … Article Volasertib suppresses the growth of human ... a potent small molecular inhibitor of polo-like kinase 1 ... 0.1% sodium

The Roles of Polo-like kinase A in Cell Cycle …iii Abstract The Roles of Polo-Like Kinase A in Cell Cycle Regulation and Development in Aspergillus nidulans Klarita Mogilevsky The

SolutionConformationsandDynamicsofABL Kinase ... · SolutionConformationsandDynamicsofABL Kinase-InhibitorComplexesDeterminedbyNMR SubstantiatetheDifferentBindingModesof Imatinib/NilotinibandDasatinib*

Hierarchical recruitment of Plk4 and regulation of centriole ...Plk4 under thymidine (S phase)- and nocodazole (M phase)-treated conditions (SI Appendix, Fig. S1B), suggesting that

PKA (Protein Kinase A) - BioSupplyNetbiosupplynet.com/kits/Protein_Kinase_A_Activity_Kit.pdf · protein kinase from rabbit skeletal muscle.”, ... protein kinase A”., ... such

Rice Mitogen Activated Protein Kinase Kinase and Mitogen