Human Sirtuin Regulators: The “Success” Stories
The human sirtuins are a group of NAD+-dependent protein deacylases. They “erase” acyl modifications from lysine residues in various cellular targets including histones, transcription factors, and metabolic enzymes. Through these far-reaching activities, sirtuins regulate a diverse array of biologic...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Physiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2021.752117/full |
| _version_ | 1818742478509965312 |
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| author | Alyson M. Curry Dawanna S. White Dickson Donu Yana Cen Yana Cen |
| author_facet | Alyson M. Curry Dawanna S. White Dickson Donu Yana Cen Yana Cen |
| author_sort | Alyson M. Curry |
| collection | DOAJ |
| description | The human sirtuins are a group of NAD+-dependent protein deacylases. They “erase” acyl modifications from lysine residues in various cellular targets including histones, transcription factors, and metabolic enzymes. Through these far-reaching activities, sirtuins regulate a diverse array of biological processes ranging from gene transcription to energy metabolism. Human sirtuins have been intensely pursued by both academia and industry as therapeutic targets for a broad spectrum of diseases such as cancer, neurodegenerative diseases, and metabolic disorders. The last two decades have witnessed a flood of small molecule sirtuin regulators. However, there remain relatively few compounds targeting human sirtuins in clinical development. This reflects the inherent issues concerning the development of isoform-selective and potent molecules with good drug-like properties. In this article, small molecule sirtuin regulators that have advanced into clinical trials will be discussed in details as “successful” examples for future drug development. Special attention is given to the discovery of these compounds, the mechanism of action, pharmacokinetics analysis, formulation, as well as the clinical outcomes observed in the trials. |
| first_indexed | 2024-12-18T02:13:09Z |
| format | Article |
| id | doaj.art-62f83a3e049348f7bcd259da06561049 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-18T02:13:09Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-62f83a3e049348f7bcd259da065610492022-12-21T21:24:26ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2021-10-011210.3389/fphys.2021.752117752117Human Sirtuin Regulators: The “Success” StoriesAlyson M. Curry0Dawanna S. White1Dickson Donu2Yana Cen3Yana Cen4Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA, United StatesDepartment of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA, United StatesDepartment of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA, United StatesDepartment of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA, United StatesInstitute for Structural Biology, Drug Discovery and Development, Virginia Commonwealth University, Richmond, VA, United StatesThe human sirtuins are a group of NAD+-dependent protein deacylases. They “erase” acyl modifications from lysine residues in various cellular targets including histones, transcription factors, and metabolic enzymes. Through these far-reaching activities, sirtuins regulate a diverse array of biological processes ranging from gene transcription to energy metabolism. Human sirtuins have been intensely pursued by both academia and industry as therapeutic targets for a broad spectrum of diseases such as cancer, neurodegenerative diseases, and metabolic disorders. The last two decades have witnessed a flood of small molecule sirtuin regulators. However, there remain relatively few compounds targeting human sirtuins in clinical development. This reflects the inherent issues concerning the development of isoform-selective and potent molecules with good drug-like properties. In this article, small molecule sirtuin regulators that have advanced into clinical trials will be discussed in details as “successful” examples for future drug development. Special attention is given to the discovery of these compounds, the mechanism of action, pharmacokinetics analysis, formulation, as well as the clinical outcomes observed in the trials.https://www.frontiersin.org/articles/10.3389/fphys.2021.752117/fullsirtuininhibitoractivatorclinical trialdrug development |
| spellingShingle | Alyson M. Curry Dawanna S. White Dickson Donu Yana Cen Yana Cen Human Sirtuin Regulators: The “Success” Stories Frontiers in Physiology sirtuin inhibitor activator clinical trial drug development |
| title | Human Sirtuin Regulators: The “Success” Stories |
| title_full | Human Sirtuin Regulators: The “Success” Stories |
| title_fullStr | Human Sirtuin Regulators: The “Success” Stories |
| title_full_unstemmed | Human Sirtuin Regulators: The “Success” Stories |
| title_short | Human Sirtuin Regulators: The “Success” Stories |
| title_sort | human sirtuin regulators the success stories |
| topic | sirtuin inhibitor activator clinical trial drug development |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2021.752117/full |
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