Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

Regulation of the Unfolded Protein Response

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...

Covalently Linked Protein Regulators

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....

Telomeres and Telomerase

Telomeres and Telomerase

In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3’ end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded...

Negative Regulator Molecules

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.

Somatic to iPS Cell Reprogramming

Somatic to iPS Cell Reprogramming

Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012...

Master Transcription Regulators

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

Enzymatic Synthesis of NAD<sup></sup>.

Current protocols·2026

Same author

Facile Synthesis of H-L-Photo-Lysine and Its Genetic Incorporation Into Proteins.

Chembiochem : a European journal of chemical biology·2026

Same author

Curcumin suppresses HNSCC tumorigenesis through directly targeting FOSL1/JUN.

Biochimica et biophysica acta. Molecular basis of disease·2026

Same author

Synaptogyrin-3 plays a critical role in addiction-related dopamine dysfunction and behavioral maladaptations.

Proceedings of the National Academy of Sciences of the United States of America·2026

Same author

Sirtuins in Women's Health.

Pharmaceuticals (Basel, Switzerland)·2025

Same author

Basic Science and Pathogenesis.

Alzheimer's & dementia : the journal of the Alzheimer's Association·2025

Search research articles

Related Experiment Video

Updated: Oct 14, 2025

Deacetylation Assays to Unravel the Interplay between Sirtuins SIRT2 and Specific Protein-substrates

Deacetylation Assays to Unravel the Interplay between Sirtuins SIRT2 and Specific Protein-substrates

Published on: February 27, 2016

Human Sirtuin Regulators: The "Success" Stories.

Alyson M Curry¹, Dawanna S White¹, Dickson Donu¹

¹Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA, United States.

Frontiers in Physiology

|November 8, 2021

Summary

This summary is machine-generated.

Human sirtuins, NAD+-dependent enzymes, regulate key biological processes. This review highlights successful small molecule regulators that have advanced into clinical trials for various diseases.

Keywords:

activator clinical trial drug development inhibitor sirtuin

More Related Videos

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

siRNA Screening to Identify Ubiquitin and Ubiquitin-like System Regulators of Biological Pathways in Cultured Mammalian Cells

siRNA Screening to Identify Ubiquitin and Ubiquitin-like System Regulators of Biological Pathways in Cultured Mammalian Cells

Published on: May 24, 2014

Related Experiment Videos

Last Updated: Oct 14, 2025

Deacetylation Assays to Unravel the Interplay between Sirtuins SIRT2 and Specific Protein-substrates

Deacetylation Assays to Unravel the Interplay between Sirtuins SIRT2 and Specific Protein-substrates

Published on: February 27, 2016

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

siRNA Screening to Identify Ubiquitin and Ubiquitin-like System Regulators of Biological Pathways in Cultured Mammalian Cells

siRNA Screening to Identify Ubiquitin and Ubiquitin-like System Regulators of Biological Pathways in Cultured Mammalian Cells

Published on: May 24, 2014

Area of Science:

Biochemistry
Molecular Biology
Pharmacology

Background:

Human sirtuins are NAD+-dependent protein deacylases regulating gene transcription and metabolism.
They are therapeutic targets for cancer, neurodegenerative, and metabolic disorders.
Despite extensive research, few small molecule sirtuin regulators have reached clinical development due to selectivity and drug-like property challenges.

Purpose of the Study:

To review small molecule sirtuin regulators that have entered clinical trials.
To provide insights into successful drug development strategies for sirtuin targets.

Main Methods:

Literature review of clinical trial data for sirtuin modulators.
Analysis of compound discovery, mechanism of action, pharmacokinetics, and formulation.
Evaluation of clinical outcomes for advanced compounds.

Main Results:

Several small molecule sirtuin regulators have progressed into clinical trials.
Challenges in developing isoform-selective and potent drugs with favorable properties persist.
Clinical outcomes provide valuable data for future therapeutic development.

Conclusions:

Small molecule sirtuin regulators show promise as therapeutics for various diseases.
Understanding the journey of compounds in clinical trials is crucial for future drug discovery.
Further research is needed to overcome development hurdles and optimize sirtuin-targeted therapies.