Literature DB >> 25589925

Fragment-based discovery of type I inhibitors of maternal embryonic leucine zipper kinase.

Christopher N Johnson1, Valerio Berdini1, Lijs Beke2, Pascal Bonnet2, Dirk Brehmer2, Joseph E Coyle1, Phillip J Day1, Martyn Frederickson1, Eddy J E Freyne2, Ron A H J Gilissen2, Christopher C F Hamlett1, Steven Howard1, Lieven Meerpoel2, Rachel McMenamin1, Sahil Patel1, David C Rees1, Andrew Sharff1, François Sommen2, Tongfei Wu2, Joannes T M Linders2.   

Abstract

Fragment-based drug design was successfully applied to maternal embryonic leucine zipper kinase (MELK). A low affinity (160 μM) fragment hit was identified, which bound to the hinge region with an atypical binding mode, and this was optimized using structure-based design into a low-nanomolar and cell-penetrant inhibitor, with a good selectivity profile, suitable for use as a chemical probe for elucidation of MELK biology.

Entities:  

Keywords:  Maternal embryonic leucine zipper kinase; fragment-based drug design; structure-based optimization

Year:  2014        PMID： 25589925      PMCID： PMC4291735          DOI： 10.1021/ml5001245

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  31 in total

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Review 2.  Ba/F3 cells and their use in kinase drug discovery.

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3.  Torsion angle preferences in druglike chemical space: a comprehensive guide.

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4.  Substrate specificity and activity regulation of protein kinase MELK.

Authors:  Monique Beullens; Sadia Vancauwenbergh; Nick Morrice; Rita Derua; Hugo Ceulemans; Etienne Waelkens; Mathieu Bollen
Journal:  J Biol Chem       Date:  2005-10-10       Impact factor: 5.157

5.  Establishment and characterization of 13 human colorectal carcinoma cell lines: mutations of genes and expressions of drug-sensitivity genes and cancer stem cell markers.

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Journal:  Carcinogenesis       Date:  2010-02-22       Impact factor: 4.944

6.  Novel inhibitor discovery through virtual screening against multiple protein conformations generated via ligand-directed modeling: a maternal embryonic leucine zipper kinase example.

Authors:  Kiran V Mahasenan; Chenglong Li
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7.  Structural basis for compound C inhibition of the human AMP-activated protein kinase α2 subunit kinase domain.

Authors:  Noriko Handa; Tetsuo Takagi; Shinya Saijo; Seiichiro Kishishita; Daisuke Takaya; Mitsutoshi Toyama; Takaho Terada; Mikako Shirouzu; Atsushi Suzuki; Suni Lee; Toshimasa Yamauchi; Miki Okada-Iwabu; Masato Iwabu; Takashi Kadowaki; Yasuhiko Minokoshi; Shigeyuki Yokoyama
Journal:  Acta Crystallogr D Biol Crystallogr       Date:  2011-04-14

8.  Maternal embryonic leucine zipper kinase/murine protein serine-threonine kinase 38 is a promising therapeutic target for multiple cancers.

Authors:  Daniel Gray; Adrian M Jubb; Deborah Hogue; Patrick Dowd; Noelyn Kljavin; Sothy Yi; Wei Bai; Gretchen Frantz; Zemin Zhang; Hartmut Koeppen; Frederic J de Sauvage; David P Davis
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Authors:  Jose M Lizcano; Olga Göransson; Rachel Toth; Maria Deak; Nick A Morrice; Jérôme Boudeau; Simon A Hawley; Lina Udd; Tomi P Mäkelä; D Grahame Hardie; Dario R Alessi
Journal:  EMBO J       Date:  2004-02-19       Impact factor: 11.598

10.  Structural basis for the regulation of maternal embryonic leucine zipper kinase.

Authors:  Lu-Sha Cao; Jue Wang; Yuling Chen; Haiteng Deng; Zhi-Xin Wang; Jia-Wei Wu
Journal:  PLoS One       Date:  2013-07-26       Impact factor: 3.240
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  11 in total

Review 1.  Enigmatic MELK: The controversy surrounding its complex role in cancer.

Authors:  Ian M McDonald; Lee M Graves
Journal:  J Biol Chem       Date:  2020-04-29       Impact factor: 5.157

2.  Fragment-Based Discovery of Potent and Selective DDR1/2 Inhibitors.

Authors:  Christopher W Murray; Valerio Berdini; Ildiko M Buck; Maria E Carr; Anne Cleasby; Joseph E Coyle; Jayne E Curry; James E H Day; Phillip J Day; Keisha Hearn; Aman Iqbal; Lydia Y W Lee; Vanessa Martins; Paul N Mortenson; Joanne M Munck; Lee W Page; Sahil Patel; Susan Roomans; Kirsten Smith; Emiliano Tamanini; Gordon Saxty
Journal:  ACS Med Chem Lett       Date:  2015-06-04       Impact factor: 4.345

3.  Arrestin-3 interaction with maternal embryonic leucine-zipper kinase.

Authors:  Nicole A Perry; Kevin P Fialkowski; Tamer S Kaoud; Ali I Kaya; Andrew L Chen; Juliana M Taliaferro; Vsevolod V Gurevich; Kevin N Dalby; T M Iverson
Journal:  Cell Signal       Date:  2019-07-25       Impact factor: 4.315

4.  Structure-Based Design of Type II Inhibitors Applied to Maternal Embryonic Leucine Zipper Kinase.

Authors:  Christopher N Johnson; Christophe Adelinet; Valerio Berdini; Lijs Beke; Pascal Bonnet; Dirk Brehmer; Frederick Calo; Joseph E Coyle; Phillip J Day; Martyn Frederickson; Eddy J E Freyne; Ron A H J Gilissen; Christopher C F Hamlett; Steven Howard; Lieven Meerpoel; Laurence Mevellec; Rachel McMenamin; Elisabeth Pasquier; Sahil Patel; David C Rees; Joannes T M Linders
Journal:  ACS Med Chem Lett       Date:  2014-05-23       Impact factor: 4.345

5.  AutoSite: an automated approach for pseudo-ligands prediction-from ligand-binding sites identification to predicting key ligand atoms.

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Review 6.  Perspective on computational and structural aspects of kinase discovery from IPK2014.

Authors:  Eric Martin; Stefan Knapp; Richard A Engh; Henrik Moebitz; Thibault Varin; Benoit Roux; Jens Meiler; Valerio Berdini; Alexander Baumann; Michal Vieth
Journal:  Biochim Biophys Acta       Date:  2015-04-07

7.  Consensus Virtual Screening Identified [1,2,4]Triazolo[1,5-b]isoquinolines As MELK Inhibitor Chemotypes.

Authors:  Anita Rácz; Roberta Palkó; Dorottya Csányi; Zsuzsanna Riedl; Dávid Bajusz; György M Keserű
Journal:  ChemMedChem       Date:  2021-10-19       Impact factor: 3.540

8.  MELK-T1, a small-molecule inhibitor of protein kinase MELK, decreases DNA-damage tolerance in proliferating cancer cells.

Authors:  Lijs Beke; Cenk Kig; Joannes T M Linders; Shannah Boens; An Boeckx; Erika van Heerde; Marc Parade; An De Bondt; Ilse Van den Wyngaert; Tarig Bashir; Souichi Ogata; Lieven Meerpoel; Aleyde Van Eynde; Christopher N Johnson; Monique Beullens; Dirk Brehmer; Mathieu Bollen
Journal:  Biosci Rep       Date:  2015-10-02       Impact factor: 3.840

9.  MELK is not necessary for the proliferation of basal-like breast cancer cells.

Authors:  Hai-Tsang Huang; Hyuk-Soo Seo; Tinghu Zhang; Yubao Wang; Baishan Jiang; Qing Li; Dennis L Buckley; Behnam Nabet; Justin M Roberts; Joshiawa Paulk; Shiva Dastjerdi; Georg E Winter; Hilary McLauchlan; Jennifer Moran; James E Bradner; Michael J Eck; Sirano Dhe-Paganon; Jean J Zhao; Nathanael S Gray
Journal:  Elife       Date:  2017-09-19       Impact factor: 8.140

10.  CRISPR/Cas9 mutagenesis invalidates a putative cancer dependency targeted in on-going clinical trials.

Authors:  Ann Lin; Christopher J Giuliano; Nicole M Sayles; Jason M Sheltzer
Journal:  Elife       Date:  2017-03-24       Impact factor: 8.140
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