Nicotinamide N-methyl transferase (NNMT): An emerging therapeutic target
•Nicotinamide N-methyltransferase (NNMT) methylates nicotinamide (vitamin B3).•Interest in NNMT as a therapeutic target has grown significantly in recent years.•NNMT overexpression is linked to cancer, metabolic disorders, and neurodegeneration.•Progress has been made in developing potent and select...
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| Veröffentlicht in: | Drug discovery today 2021-11, Vol.26 (11), p.2699-2706 |
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| creator | Gao, Yongzhi Martin, Nathaniel I. van Haren, Matthijs J. |
| description | •Nicotinamide N-methyltransferase (NNMT) methylates nicotinamide (vitamin B3).•Interest in NNMT as a therapeutic target has grown significantly in recent years.•NNMT overexpression is linked to cancer, metabolic disorders, and neurodegeneration.•Progress has been made in developing potent and selective NNMT inhibitors.•Most NNMT inhibitors described to date display limited in vivo activity.
Nicotinamide N-methyltransferase (NNMT) methylates nicotinamide (NA) to generate 1-methyl nicotinamide. Since its discovery 70 years ago, the appreciation of the role of NNMT in human health has evolved from serving only metabolic functions to also being a driving force in diseases, including a variety of cancers. Despite the increasing evidence indicating NNMT as a viable therapeutic target, the development of cell-active inhibitors against this enzyme is lacking. In this review, we provide an overview of the current status of NNMT inhibitor development, relevant in vitro and in vivo studies, and a discussion of the challenges faced in the development of NNMT inhibitors. |
| doi_str_mv | 10.1016/j.drudis.2021.05.011 |
| format | Article |
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Nicotinamide N-methyltransferase (NNMT) methylates nicotinamide (NA) to generate 1-methyl nicotinamide. Since its discovery 70 years ago, the appreciation of the role of NNMT in human health has evolved from serving only metabolic functions to also being a driving force in diseases, including a variety of cancers. Despite the increasing evidence indicating NNMT as a viable therapeutic target, the development of cell-active inhibitors against this enzyme is lacking. In this review, we provide an overview of the current status of NNMT inhibitor development, relevant in vitro and in vivo studies, and a discussion of the challenges faced in the development of NNMT inhibitors.</description><identifier>ISSN: 1359-6446</identifier><identifier>EISSN: 1878-5832</identifier><identifier>DOI: 10.1016/j.drudis.2021.05.011</identifier><identifier>PMID: 34029690</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Cancer ; Enzyme Inhibitors - therapeutic use ; Humans ; Inhibitors ; Metabolic Diseases - drug therapy ; Metabolic Diseases - metabolism ; Metabolic disorder ; Neoplasms - drug therapy ; Neoplasms - metabolism ; Neurodegenerative disease ; Neurodegenerative Diseases - drug therapy ; Neurodegenerative Diseases - metabolism ; Niacinamide - analogs & derivatives ; Niacinamide - metabolism ; Nicotinamide ; Nicotinamide N-Methyltransferase - antagonists & inhibitors ; Nicotinamide N-Methyltransferase - metabolism ; NNMT ; S-adenosyl-l-methionine ; S-Adenosylmethionine - metabolism</subject><ispartof>Drug discovery today, 2021-11, Vol.26 (11), p.2699-2706</ispartof><rights>2021 The Author(s)</rights><rights>Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c408t-5eb79523e18b8630a900e68e5c7eec07b431bd276d7a621a0c7babc7f08f20e3</citedby><cites>FETCH-LOGICAL-c408t-5eb79523e18b8630a900e68e5c7eec07b431bd276d7a621a0c7babc7f08f20e3</cites><orcidid>0000-0001-8246-3006</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1359644621002427$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34029690$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gao, Yongzhi</creatorcontrib><creatorcontrib>Martin, Nathaniel I.</creatorcontrib><creatorcontrib>van Haren, Matthijs J.</creatorcontrib><title>Nicotinamide N-methyl transferase (NNMT): An emerging therapeutic target</title><title>Drug discovery today</title><addtitle>Drug Discov Today</addtitle><description>•Nicotinamide N-methyltransferase (NNMT) methylates nicotinamide (vitamin B3).•Interest in NNMT as a therapeutic target has grown significantly in recent years.•NNMT overexpression is linked to cancer, metabolic disorders, and neurodegeneration.•Progress has been made in developing potent and selective NNMT inhibitors.•Most NNMT inhibitors described to date display limited in vivo activity.
Nicotinamide N-methyltransferase (NNMT) methylates nicotinamide (NA) to generate 1-methyl nicotinamide. Since its discovery 70 years ago, the appreciation of the role of NNMT in human health has evolved from serving only metabolic functions to also being a driving force in diseases, including a variety of cancers. Despite the increasing evidence indicating NNMT as a viable therapeutic target, the development of cell-active inhibitors against this enzyme is lacking. In this review, we provide an overview of the current status of NNMT inhibitor development, relevant in vitro and in vivo studies, and a discussion of the challenges faced in the development of NNMT inhibitors.</description><subject>Cancer</subject><subject>Enzyme Inhibitors - therapeutic use</subject><subject>Humans</subject><subject>Inhibitors</subject><subject>Metabolic Diseases - drug therapy</subject><subject>Metabolic Diseases - metabolism</subject><subject>Metabolic disorder</subject><subject>Neoplasms - drug therapy</subject><subject>Neoplasms - metabolism</subject><subject>Neurodegenerative disease</subject><subject>Neurodegenerative Diseases - drug therapy</subject><subject>Neurodegenerative Diseases - metabolism</subject><subject>Niacinamide - analogs & derivatives</subject><subject>Niacinamide - metabolism</subject><subject>Nicotinamide</subject><subject>Nicotinamide N-Methyltransferase - antagonists & inhibitors</subject><subject>Nicotinamide N-Methyltransferase - metabolism</subject><subject>NNMT</subject><subject>S-adenosyl-l-methionine</subject><subject>S-Adenosylmethionine - metabolism</subject><issn>1359-6446</issn><issn>1878-5832</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1LxDAQhoMofqz-A5Ee9dA6SZuk9SAsi7rCul72HtJ0umbpx5qkgv_eStWjh2EG5n3nZR5CLikkFKi43SWVGyrrEwaMJsAToPSAnNJc5jHPU3Y4zikvYpFl4oSceb8DoKzg4picpBmwQhRwSpZra_pgO93aCqN13GJ4-2yi4HTna3TaY3S9Xr9sbu6ieRdhi25ru20U3sbdHodgTRS022I4J0e1bjxe_PQZ2Tw-bBbLePX69LyYr2KTQR5ijqUsOEuR5mUuUtAFAIocuZGIBmSZpbSsmBSV1IJRDUaWujSyhrxmgOmMXE9n965_H9AH1VpvsGl0h_3gFeMpG0uKYpRmk9S43nuHtdo722r3qSiob4RqpyaE6huhAq5GhKPt6idhKFus_ky_zEbB_STA8c0Pi055Y7EzWFmHJqiqt_8nfAEvUIOM</recordid><startdate>202111</startdate><enddate>202111</enddate><creator>Gao, Yongzhi</creator><creator>Martin, Nathaniel I.</creator><creator>van Haren, Matthijs J.</creator><general>Elsevier Ltd</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-8246-3006</orcidid></search><sort><creationdate>202111</creationdate><title>Nicotinamide N-methyl transferase (NNMT): An emerging therapeutic target</title><author>Gao, Yongzhi ; Martin, Nathaniel I. ; van Haren, Matthijs J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c408t-5eb79523e18b8630a900e68e5c7eec07b431bd276d7a621a0c7babc7f08f20e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Cancer</topic><topic>Enzyme Inhibitors - therapeutic use</topic><topic>Humans</topic><topic>Inhibitors</topic><topic>Metabolic Diseases - drug therapy</topic><topic>Metabolic Diseases - metabolism</topic><topic>Metabolic disorder</topic><topic>Neoplasms - drug therapy</topic><topic>Neoplasms - metabolism</topic><topic>Neurodegenerative disease</topic><topic>Neurodegenerative Diseases - drug therapy</topic><topic>Neurodegenerative Diseases - metabolism</topic><topic>Niacinamide - analogs & derivatives</topic><topic>Niacinamide - metabolism</topic><topic>Nicotinamide</topic><topic>Nicotinamide N-Methyltransferase - antagonists & inhibitors</topic><topic>Nicotinamide N-Methyltransferase - metabolism</topic><topic>NNMT</topic><topic>S-adenosyl-l-methionine</topic><topic>S-Adenosylmethionine - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gao, Yongzhi</creatorcontrib><creatorcontrib>Martin, Nathaniel I.</creatorcontrib><creatorcontrib>van Haren, Matthijs J.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Drug discovery today</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gao, Yongzhi</au><au>Martin, Nathaniel I.</au><au>van Haren, Matthijs J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nicotinamide N-methyl transferase (NNMT): An emerging therapeutic target</atitle><jtitle>Drug discovery today</jtitle><addtitle>Drug Discov Today</addtitle><date>2021-11</date><risdate>2021</risdate><volume>26</volume><issue>11</issue><spage>2699</spage><epage>2706</epage><pages>2699-2706</pages><issn>1359-6446</issn><eissn>1878-5832</eissn><abstract>•Nicotinamide N-methyltransferase (NNMT) methylates nicotinamide (vitamin B3).•Interest in NNMT as a therapeutic target has grown significantly in recent years.•NNMT overexpression is linked to cancer, metabolic disorders, and neurodegeneration.•Progress has been made in developing potent and selective NNMT inhibitors.•Most NNMT inhibitors described to date display limited in vivo activity.
Nicotinamide N-methyltransferase (NNMT) methylates nicotinamide (NA) to generate 1-methyl nicotinamide. Since its discovery 70 years ago, the appreciation of the role of NNMT in human health has evolved from serving only metabolic functions to also being a driving force in diseases, including a variety of cancers. Despite the increasing evidence indicating NNMT as a viable therapeutic target, the development of cell-active inhibitors against this enzyme is lacking. In this review, we provide an overview of the current status of NNMT inhibitor development, relevant in vitro and in vivo studies, and a discussion of the challenges faced in the development of NNMT inhibitors.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>34029690</pmid><doi>10.1016/j.drudis.2021.05.011</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0001-8246-3006</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Cancer Enzyme Inhibitors - therapeutic use Humans Inhibitors Metabolic Diseases - drug therapy Metabolic Diseases - metabolism Metabolic disorder Neoplasms - drug therapy Neoplasms - metabolism Neurodegenerative disease Neurodegenerative Diseases - drug therapy Neurodegenerative Diseases - metabolism Niacinamide - analogs & derivatives Niacinamide - metabolism Nicotinamide Nicotinamide N-Methyltransferase - antagonists & inhibitors Nicotinamide N-Methyltransferase - metabolism NNMT S-adenosyl-l-methionine S-Adenosylmethionine - metabolism |
| title | Nicotinamide N-methyl transferase (NNMT): An emerging therapeutic target |
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