Literature DB >> 27994746

Turning a Substrate Peptide into a Potent Inhibitor for the Histone Methyltransferase SETD8.

Russell A Judge1, Haizhong Zhu1, Anup K Upadhyay1, Pierre M Bodelle1, Charles W Hutchins1, Maricel Torrent1, Violeta L Marin1, Wenyu Yu2, Masoud Vedadi2, Fengling Li2, Peter J Brown2, William N Pappano1, Chaohong Sun1, Andrew M Petros1.   

Abstract

SETD8 is a histone H4-K20 methyltransferase that plays an essential role in the maintenance of genomic integrity during mitosis and in DNA damage repair, making it an intriguing target for cancer research. While some small molecule inhibitors for SETD8 have been reported, the structural binding modes for these inhibitors have not been revealed. Using the complex structure of the substrate peptide bound to SETD8 as a starting point, different natural and unnatural amino acid substitutions were tested, and a potent (Ki 50 nM, IC50 0.33 μM) and selective norleucine containing peptide inhibitor has been obtained.

Entities:  

Keywords:  HMT; SETD8; cancer; drug design; structure-based drug design

Year:  2016        PMID： 27994746      PMCID： PMC5150682          DOI： 10.1021/acsmedchemlett.6b00303

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


  24 in total

1.  SET8 promotes epithelial-mesenchymal transition and confers TWIST dual transcriptional activities.

Authors:  Fen Yang; Luyang Sun; Qian Li; Xiao Han; Liandi Lei; Hua Zhang; Yongfeng Shang
Journal:  EMBO J       Date:  2011-10-07       Impact factor: 11.598

Review 2.  PR-Set7 and H4K20me1: at the crossroads of genome integrity, cell cycle, chromosome condensation, and transcription.

Authors:  David B Beck; Hisanobu Oda; Steven S Shen; Danny Reinberg
Journal:  Genes Dev       Date:  2012-02-15       Impact factor: 11.361

3.  Identification of PR-SET7 and EZH2 selective inhibitors inducing cell death in human leukemia U937 cells.

Authors:  Sergio Valente; Ilaria Lepore; Carmela Dell'Aversana; Maria Tardugno; Sabrina Castellano; Gianluca Sbardella; Stefano Tomassi; Salvatore Di Maro; Ettore Novellino; Roberto Di Santo; Roberta Costi; Lucia Altucci; Antonello Mai
Journal:  Biochimie       Date:  2012-06-16       Impact factor: 4.079

4.  Discovery of A-893, A New Cell-Active Benzoxazinone Inhibitor of Lysine Methyltransferase SMYD2.

Authors:  Ramzi F Sweis; Zhi Wang; Mikkel Algire; Cheryl H Arrowsmith; Peter J Brown; Gary G Chiang; Jun Guo; Clarissa G Jakob; Steven Kennedy; Fengling Li; David Maag; Bailin Shaw; Nirupama B Soni; Masoud Vedadi; William N Pappano
Journal:  ACS Med Chem Lett       Date:  2015-04-29       Impact factor: 4.345

5.  Nahuoic acid A produced by a Streptomyces sp. isolated from a marine sediment is a selective SAM-competitive inhibitor of the histone methyltransferase SETD8.

Authors:  David E Williams; Doralyn S Dalisay; Fengling Li; James Amphlett; Wisanu Maneerat; Miguel Angel Garcia Chavez; Yan Alexander Wang; Teatulohi Matainaho; Wenyu Yu; Peter J Brown; Cheryl H Arrowsmith; Masoud Vedadi; Raymond J Andersen
Journal:  Org Lett       Date:  2012-12-28       Impact factor: 6.005

6.  Catalytic site remodelling of the DOT1L methyltransferase by selective inhibitors.

Authors:  Wenyu Yu; Emma J Chory; Amy K Wernimont; Wolfram Tempel; Alex Scopton; Alexander Federation; Jason J Marineau; Jun Qi; Dalia Barsyte-Lovejoy; Joanna Yi; Richard Marcellus; Roxana E Iacob; John R Engen; Carly Griffin; Ahmed Aman; Erno Wienholds; Fengling Li; Javier Pineda; Guillermina Estiu; Tatiana Shatseva; Taraneh Hajian; Rima Al-Awar; John E Dick; Masoud Vedadi; Peter J Brown; Cheryl H Arrowsmith; James E Bradner; Matthieu Schapira
Journal:  Nat Commun       Date:  2012       Impact factor: 14.919

7.  Arginine topology controls escape of minimally cationic proteins from early endosomes to the cytoplasm.

Authors:  Jacob S Appelbaum; Jonathan R LaRochelle; Betsy A Smith; Daniel M Balkin; Justin M Holub; Alanna Schepartz
Journal:  Chem Biol       Date:  2012-07-27

8.  Design and synthesis of statine-based cell-permeable peptidomimetic inhibitors of human beta-secretase.

Authors:  Roy K Hom; Larry Y Fang; Shumeye Mamo; Jay S Tung; Ashley C Guinn; Don E Walker; David L Davis; Andrea F Gailunas; Eugene D Thorsett; Sukanto Sinha; Jeroen E Knops; Nancy E Jewett; John P Anderson; Varghese John
Journal:  J Med Chem       Date:  2003-05-08       Impact factor: 7.446

9.  Modulation of p53 function by SET8-mediated methylation at lysine 382.

Authors:  Xiaobing Shi; Ioulia Kachirskaia; Hiroshi Yamaguchi; Lisandra E West; Hong Wen; Evelyn W Wang; Sucharita Dutta; Ettore Appella; Or Gozani
Journal:  Mol Cell       Date:  2007-08-17       Impact factor: 17.970

10.  Inhibiting complex IL-17A and IL-17RA interactions with a linear peptide.

Authors:  Shenping Liu; Joel Desharnais; Parag V Sahasrabudhe; Ping Jin; Wei Li; Bryan D Oates; Suman Shanker; Mary Ellen Banker; Boris A Chrunyk; Xi Song; Xidong Feng; Matt Griffor; Judith Jimenez; Gang Chen; David Tumelty; Abhijit Bhat; Curt W Bradshaw; Gary Woodnutt; Rodney W Lappe; Atli Thorarensen; Xiayang Qiu; Jane M Withka; Lauren D Wood
Journal:  Sci Rep       Date:  2016-05-17       Impact factor: 4.379
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  5 in total

Review 1.  Inhibitors of Protein Methyltransferases and Demethylases.

Authors:  H Ümit Kaniskan; Michael L Martini; Jian Jin
Journal:  Chem Rev       Date:  2017-03-24       Impact factor: 60.622

Review 2.  Clinically Applicable Inhibitors Impacting Genome Stability.

Authors:  Anu Prakash; Juan F Garcia-Moreno; James A L Brown; Emer Bourke
Journal:  Molecules       Date:  2018-05-13       Impact factor: 4.411

3.  Histone lysine methyltransferase structure activity relationships that allow for segregation of G9a inhibition and anti-Plasmodium activity.

Authors:  Sandeep Sundriyal; Patty B Chen; Alexandra S Lubin; Gregor A Lueg; Fengling Li; Andrew J P White; Nicholas A Malmquist; Masoud Vedadi; Artur Scherf; Matthew J Fuchter
Journal:  Medchemcomm       Date:  2017-03-15       Impact factor: 3.597

Review 4.  The Promise for Histone Methyltransferase Inhibitors for Epigenetic Therapy in Clinical Oncology: A Narrative Review.

Authors:  Hope S Rugo; Ira Jacobs; Shikhar Sharma; Frank Scappaticci; Thomas A Paul; Kristen Jensen-Pergakes; Gabriel G Malouf
Journal:  Adv Ther       Date:  2020-05-22       Impact factor: 3.845

5.  Identification of a peptide inhibitor for the histone methyltransferase WHSC1.

Authors:  Michael J Morrison; P Ann Boriack-Sjodin; Kerren K Swinger; Tim J Wigle; Dipti Sadalge; Kevin W Kuntz; Margaret Porter Scott; William P Janzen; Richard Chesworth; Kenneth W Duncan; Darren M Harvey; John W Lampe; Lorna H Mitchell; Robert A Copeland
Journal:  PLoS One       Date:  2018-05-09       Impact factor: 3.240
  5 in total

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