Literature DB >> 33668468

Novel Inhibitors of Nicotinamide-N-Methyltransferase for the Treatment of Metabolic Disorders.

Aimo Kannt1, Sridharan Rajagopal2, Mahanandeesha S Hallur2, Indu Swamy2, Rajendra Kristam2, Saravanakumar Dhakshinamoorthy2, Joerg Czech3, Gernot Zech3, Herman Schreuder3, Sven Ruf3.   

Abstract

Nicotinamide-N-methyltransferase (NNMT) is a cytosolic enzyme catalyzing the transfer of a methyl group from S-adenosyl-methionine (SAM) to nicotinamide (Nam). It is expressed in many tissues including the liver, adipose tissue, and skeletal muscle. Its expression in several cancer cell lines has been widely discussed in the literature, and recent work established a link between NNMT expression and metabolic diseases. Here we describe our approach to identify potent small molecule inhibitors of NNMT featuring different binding modes as elucidated by X-ray crystallographic studies.

Entities:  

Keywords:  X-ray; metabolic disease; nicotinamide; nicotinamide-N-methyltransferase; small molecule inhibitor

Mesh：

Substances：

Year:  2021        PMID： 33668468      PMCID： PMC7918612          DOI： 10.3390/molecules26040991

Source DB:  PubMed          Journal:  Molecules        ISSN： 1420-3049            Impact factor:   4.411


  29 in total

1.  Covalent inhibitors of nicotinamide N-methyltransferase (NNMT) provide evidence for target engagement challenges in situ.

Authors:  Hsin-Yu Lee; Radu M Suciu; Benjamin D Horning; Ekaterina V Vinogradova; Olesya A Ulanovskaya; Benjamin F Cravatt
Journal:  Bioorg Med Chem Lett       Date:  2018-04-10       Impact factor: 2.823

2.  Structural basis of substrate recognition in human nicotinamide N-methyltransferase.

Authors:  Yi Peng; Davide Sartini; Valentina Pozzi; Dennis Wilk; Monica Emanuelli; Vivien C Yee
Journal:  Biochemistry       Date:  2011-08-17       Impact factor: 3.162

3.  Inhibitors of nicotinamide N-methyltransferase designed to mimic the methylation reaction transition state.

Authors:  Matthijs J van Haren; Rebecca Taig; Jilles Kuppens; Javier Sastre Toraño; Ed E Moret; Richard B Parsons; Davide Sartini; Monica Emanuelli; Nathaniel I Martin
Journal:  Org Biomol Chem       Date:  2017-08-09       Impact factor: 3.876

4.  Discovery of Bisubstrate Inhibitors of Nicotinamide N-Methyltransferase (NNMT).

Authors:  Nicolas Babault; Abdellah Allali-Hassani; Fengling Li; Jie Fan; Alex Yue; Kevin Ju; Feng Liu; Masoud Vedadi; Jing Liu; Jian Jin
Journal:  J Med Chem       Date:  2018-01-31       Impact factor: 7.446

5.  Microarray profiling of isolated abdominal subcutaneous adipocytes from obese vs non-obese Pima Indians: increased expression of inflammation-related genes.

Authors:  Y H Lee; S Nair; E Rousseau; D B Allison; G P Page; P A Tataranni; C Bogardus; P A Permana
Journal:  Diabetologia       Date:  2005-07-30       Impact factor: 10.122

6.  Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase reverse high fat diet-induced obesity in mice.

Authors:  Harshini Neelakantan; Virginia Vance; Michael D Wetzel; Hua-Yu Leo Wang; Stanton F McHardy; Celeste C Finnerty; Jonathan D Hommel; Stanley J Watowich
Journal:  Biochem Pharmacol       Date:  2017-11-15       Impact factor: 5.858

7.  High-Affinity Alkynyl Bisubstrate Inhibitors of Nicotinamide N-Methyltransferase (NNMT).

Authors:  Rocco L Policarpo; Ludovic Decultot; Elizabeth May; Petr Kuzmič; Samuel Carlson; Danny Huang; Vincent Chu; Brandon A Wright; Saravanakumar Dhakshinamoorthy; Aimo Kannt; Shilpa Rani; Sreekanth Dittakavi; Joseph D Panarese; Rachelle Gaudet; Matthew D Shair
Journal:  J Med Chem       Date:  2019-10-25       Impact factor: 7.446

8.  Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity.

Authors:  Daniel Kraus; Qin Yang; Dong Kong; Alexander S Banks; Lin Zhang; Joseph T Rodgers; Eija Pirinen; Thomas C Pulinilkunnil; Fengying Gong; Ya-chin Wang; Yana Cen; Anthony A Sauve; John M Asara; Odile D Peroni; Brett P Monia; Sanjay Bhanot; Leena Alhonen; Pere Puigserver; Barbara B Kahn
Journal:  Nature       Date:  2014-04-10       Impact factor: 49.962

9.  Bisubstrate Inhibitors of Nicotinamide N-Methyltransferase (NNMT) with Enhanced Activity.

Authors:  Yongzhi Gao; Matthijs J van Haren; Ed E Moret; Johannes J M Rood; Davide Sartini; Alessia Salvucci; Monica Emanuelli; Pierrick Craveur; Nicolas Babault; Jian Jin; Nathaniel I Martin
Journal:  J Med Chem       Date:  2019-07-12       Impact factor: 7.446

10.  A small molecule inhibitor of Nicotinamide N-methyltransferase for the treatment of metabolic disorders.

Authors:  Aimo Kannt; Sridharan Rajagopal; Sanjay Venkatachalapathi Kadnur; Juluri Suresh; Ravi Kanth Bhamidipati; Srinivasan Swaminathan; Mahanandeesha Siddappa Hallur; Rajendra Kristam; Ralf Elvert; Jörg Czech; Anja Pfenninger; Christine Rudolph; Herman Schreuder; Devaraj Venkatapura Chandrasekar; Vishal Subhash Mane; Swarnakumari Birudukota; Shama Shaik; Bharat Ravindra Zope; Raghunadha Reddy Burri; Niranjan Naranapura Anand; Manish Kumar Thakur; Manvi Singh; Reejuana Parveen; Saravanan Kandan; Ramesh Mullangi; Takeshi Yura; Ramachandraiah Gosu; Sven Ruf; Saravanakumar Dhakshinamoorthy
Journal:  Sci Rep       Date:  2018-02-26       Impact factor: 4.379
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  8 in total

Review 1.  Insights into S-adenosyl-l-methionine (SAM)-dependent methyltransferase related diseases and genetic polymorphisms.

Authors:  Jiaojiao Li; Chunxiao Sun; Wenwen Cai; Jing Li; Barry P Rosen; Jian Chen
Journal:  Mutat Res Rev Mutat Res       Date:  2021-10-07       Impact factor: 7.015

2.  Nicotinamide N-methyltransferase is related to MELF pattern invasion in endometrioid carcinoma.

Authors:  Shinichiro Tahara; Satoshi Nojima; Kenji Ohshima; Yumiko Hori; Kazuaki Sato; Masako Kurashige; Takahiro Matsui; Daisuke Okuzaki; Eiichi Morii
Journal:  Cancer Med       Date:  2021-10-16       Impact factor: 4.452

Review 3.  Nicotinamide N-Methyltransferase: An Emerging Protagonist in Cancer Macro(r)evolution.

Authors:  Richard B Parsons; Paul D Facey
Journal:  Biomolecules       Date:  2021-09-28

4.  Long non-coding RNA XIST promotes osteoporosis by inhibiting the differentiation of bone marrow mesenchymal stem cell by sponging miR-29b-3p that suppresses nicotinamide N-methyltransferase.

Authors:  Jiang Yu; Min Xiao; Guohai Ren
Journal:  Bioengineered       Date:  2021-12       Impact factor: 3.269

Review 5.  Nicotinamide N-Methyltransferase: A Promising Biomarker and Target for Human Cancer Therapy.

Authors:  Xiao-Yu Li; Ya-Nan Pi; Yao Chen; Qi Zhu; Bai-Rong Xia
Journal:  Front Oncol       Date:  2022-06-09       Impact factor: 5.738

6.  Novel tricyclic small molecule inhibitors of Nicotinamide N-methyltransferase for the treatment of metabolic disorders.

Authors:  Sven Ruf; Sridharan Rajagopal; Sanjay Venkatachalapathi Kadnur; Mahanandeesha S Hallur; Shilpa Rani; Rajendra Kristam; Srinivasan Swaminathan; Bharat Ravindra Zope; Pavan Kumar Gondrala; Indu Swamy; V P Rama Kishore Putta; Saravanan Kandan; Gernot Zech; Herman Schreuder; Christine Rudolph; Ralf Elvert; Joerg Czech; Swarnakumari Birudukota; M Amir Siddiqui; Niranjan Naranapura Anand; Vishal Subhash Mane; Sreekanth Dittakavi; Juluri Suresh; Ramachandraiah Gosu; Mullangi Ramesh; Takeshi Yura; Saravanakumar Dhakshinamoorthy; Aimo Kannt
Journal:  Sci Rep       Date:  2022-09-14       Impact factor: 4.996

Review 7.  Nicotinamide N-Methyltransferase as Promising Tool for Management of Gastrointestinal Neoplasms.

Authors:  Valentina Pozzi; Roberto Campagna; Davide Sartini; Monica Emanuelli
Journal:  Biomolecules       Date:  2022-08-24

Review 8.  Complex roles of nicotinamide N-methyltransferase in cancer progression.

Authors:  Weixuan Wang; Changmei Yang; Tianxiang Wang; Haiteng Deng
Journal:  Cell Death Dis       Date:  2022-03-25       Impact factor: 9.685
  8 in total

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