Sirtuin modulators: past, present, and future perspectives

Pharmacological and genetic perturbation establish SIRT5 as a promising target in breast cancer

(2021) Yashira L. Negrón Abril et al.   ONCOGENE

SIRT1 and SIRT2 Activity Control in Neurodegenerative Diseases

(2021) Ramu Manjula et al.   Frontiers in Pharmacology

Reply to: Binding site for MDL-801 on SIRT6

(2021) Zhimin Huang et al.   Nature Chemical Biology

Binding site for activator MDL-801 on SIRT6

(2021) Weijie You et al.   Nature Chemical Biology

The Two-Faced Role of SIRT6 in Cancer

(2021) Francesco Fiorentino et al.   Cancers

Discovery of Dihydro-1,4-Benzoxazine Carboxamides as Potent and Highly Selective Inhibitors of Sirtuin-1

(2021) Martin Spinck et al.   JOURNAL OF MEDICINAL CHEMISTRY

SIRT5 Inhibition Induces Brown Fat-Like Phenotype in 3T3-L1 Preadipocytes

(2021) Francesca Molinari et al.   Cells

Metabolic Rewiring by Loss of Sirt5 Promotes Kras-Induced Pancreatic Cancer Progression

(2021) Tuo Hu et al.   GASTROENTEROLOGY

Emerging Therapeutic Potential of SIRT6 Modulators

(2021) Francesco Fiorentino et al.   JOURNAL OF MEDICINAL CHEMISTRY

Cryo-EM structure determination of small proteins by nanobody-binding scaffolds (Legobodies)

(2021) Xudong Wu et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Human Sirtuin Regulators: The “Success” Stories

(2021) Alyson M. Curry et al.   Frontiers in Physiology

Discovery of 5-(4-Methylpiperazin-1-yl)-2-nitroaniline Derivatives as A New Class of SIRT6 Inhibitors

(2020) Weining Sun et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Sirtuin modulators: where are we now? A review of patents from 2015 to 2019

(2020) Nicola Mautone et al.   EXPERT OPINION ON THERAPEUTIC PATENTS

The role of SIRT2 in cancer: a novel therapeutic target

(2020) Guangyuan Chen et al.   INTERNATIONAL JOURNAL OF CANCER

Sirt4: A Multifaceted Enzyme at the Crossroads of Mitochondrial Metabolism and Cancer

(2020) Daniela Tomaselli et al.   Frontiers in Oncology

The Pan-Sirtuin Inhibitor MC2494 Regulates Mitochondrial Function in a Leukemia Cell Line

(2020) Vincenzo Carafa et al.   Frontiers in Oncology

MDL-800, an allosteric activator of SIRT6, suppresses proliferation and enhances EGFR-TKIs therapy in non-small cell lung cancer

(2020) Jia-lin Shang et al.   ACTA PHARMACOLOGICA SINICA

RTN4B‐mediated suppression of Sirtuin 2 activity ameliorates β‐amyloid pathology and cognitive impairment in Alzheimer's disease mouse model

(2020) Yan Wang et al.   AGING CELL

HaloTag‐targeted Sirtuin rearranging ligand (SirReal) for the development of proteolysis targeting chimeras (PROTACs) against the lysine deacetylase Sirtuin 2 (Sirt2)

(2020) Matthias Schiedel et al.   CHEMBIOCHEM

Targeting histone acetylation/deacetylation in parasites: an update (2017–2020)

(2020) Rossella Fioravanti et al.   CURRENT OPINION IN CHEMICAL BIOLOGY

Thirty Years of HDAC Inhibitors: 2020 Insight and Hindsight

(2020) Terence C. S. Ho et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of Potent Small Molecule SIRT6 Activators: Structure-Activity Relationship and Anti-pancreatic Ductal Adenocarcinoma Activity

(2020) Xiuli Chen et al.   JOURNAL OF MEDICINAL CHEMISTRY

Lysine Acetyltransferase Inhibitors From Natural Sources

(2020) Francesco Fiorentino et al.   Frontiers in Pharmacology

Synthesis of indole inhibitors of silent information regulator 1 (SIRT1), and their evaluation as cytotoxic agents

(2020) Hanna Laaroussi et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

A Focused DNA-Encoded Chemical Library for the Discovery of Inhibitors of NAD+-Dependent Enzymes

(2019) Lik Hang Yuen et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Novel Lysine-Based Thioureas as Mechanism-Based Inhibitors of Sirtuin 2 (SIRT2) with Anticancer Activity in a Colorectal Cancer Murine Model

(2019) Ali Sohail Farooqi et al.   JOURNAL OF MEDICINAL CHEMISTRY

SIRT6, a Mammalian deacylase with multitasking abilities

(2019) Andrew R Chang et al.   PHYSIOLOGICAL REVIEWS

SIRT4 and Its Roles in Energy and Redox Metabolism in Health, Disease and During Exercise

(2019) Yumei Han et al.   Frontiers in Physiology

SIRT2: Controversy and multiple roles in disease and physiology

(2019) Yan Wang et al.   AGEING RESEARCH REVIEWS

Enzymatic and Biological Characterization of Novel Sirtuin Modulators against Cancer

(2019) Vincenzo Carafa et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

The Roles of Sirtuin Family Proteins in Cancer Progression

(2019) Erhu Zhao et al.   Cancers

Emerging Roles for SIRT5 in Metabolism and Cancer

(2018) Lauren R. Bringman-Rodenbarger et al.   ANTIOXIDANTS & REDOX SIGNALING

RIP1–HAT1–SIRT Complex Identification and Targeting in Treatment and Prevention of Cancer

(2018) Vincenzo Carafa et al.   CLINICAL CANCER RESEARCH

Functions of the sirtuin deacylase SIRT5 in normal physiology and pathobiology

(2018) Surinder Kumar et al.   CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY

X-ray crystal structure guided discovery of new selective, substrate-mimicking sirtuin 2 inhibitors that exhibit activities against non-small cell lung cancer cells

(2018) Ling-Ling Yang et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Sirtuin activators and inhibitors: Promises, achievements, and challenges

(2018) Han Dai et al.   PHARMACOLOGY & THERAPEUTICS

New chemical tools for probing activity and inhibition of the NAD + -dependent lysine deacylase sirtuin 2

(2018) Sören Swyter et al.   PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES

SIRT1 facilitates amyloid beta peptide degradation by upregulating lysosome number in primary astrocytes

(2018) Min-Zhe Li et al.   Neural Regeneration Research

Pharmacological activation of SIRT6 triggers lethal autophagy in human cancer cells

(2018) Sara Iachettini et al.   Cell Death & Disease

Identification of a novel SIRT7 inhibitor as anticancer drug candidate

(2018) Ji-Hye Kim et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

DNA-Encoded Dynamic Chemical Library and Its Applications in Ligand Discovery

(2018) Yu Zhou et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Identification of a cellularly active SIRT6 allosteric activator

(2018) Zhimin Huang et al.   Nature Chemical Biology

Advances in Cellular Characterization of the Sirtuin Isoform, SIRT7

(2018) Di Wu et al.   Frontiers in Endocrinology

Discovery of 2-((4,6-dimethylpyrimidin-2-yl)thio)- N -phenylacetamide derivatives as new potent and selective human sirtuin 2 inhibitors

(2017) Lingling Yang et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Development of 1,2,4-Oxadiazoles as Potent and Selective Inhibitors of the Human Deacetylase Sirtuin 2: Structure–Activity Relationship, X-ray Crystal Structure, and Anticancer Activity

(2017) Sébastien Moniot et al.   JOURNAL OF MEDICINAL CHEMISTRY

Chemically Induced Degradation of Sirtuin 2 (Sirt2) by a Proteolysis Targeting Chimera (PROTAC) Based on Sirtuin Rearranging Ligands (SirReals)

(2017) Matthias Schiedel et al.   JOURNAL OF MEDICINAL CHEMISTRY

Suppression of Sirt1 sensitizes lung cancer cells to WEE1 inhibitor MK-1775-induced DNA damage and apoptosis

(2017) G Chen et al.   ONCOGENE

SIRT6: Novel Mechanisms and Links to Aging and Disease

(2017) Luisa Tasselli et al.   TRENDS IN ENDOCRINOLOGY AND METABOLISM

Potent mechanism-based sirtuin-2-selective inhibition by an in situ-generated occupant of the substrate-binding site, “selectivity pocket” and NAD+-binding site

(2017) Paolo Mellini et al.   Chemical Science

Crystal structures of the mitochondrial deacylase Sirtuin 4 reveal isoform-specific acyl recognition and regulation features

(2017) Martin Pannek et al.   Nature Communications

Structural Basis of Sirtuin 6 Activation by Synthetic Small Molecules

(2016) Weijie You et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Structure-Based Development of an Affinity Probe for Sirtuin 2

(2016) Matthias Schiedel et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

SIRT4 regulates cancer cell survival and growth after stress

(2016) Seung Min Jeong et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

A SIRT2-Selective Inhibitor Promotes c-Myc Oncoprotein Degradation and Exhibits Broad Anticancer Activity

(2016) Hui Jing et al.   CANCER CELL

Mitochondrial SIRT3 Mediates Adaptive Responses of Neurons to Exercise and Metabolic and Excitatory Challenges

(2016) Aiwu Cheng et al.   Cell Metabolism

Crystal structures of SIRT3 reveal that the α2-α3 loop and α3-helix affect the interaction with long-chain acyl lysine

(2016) Wei Gai et al.   FEBS LETTERS

Aminothiazoles as Potent and Selective Sirt2 Inhibitors: A Structure–Activity Relationship Study

(2016) Matthias Schiedel et al.   JOURNAL OF MEDICINAL CHEMISTRY

1,4-Dihydropyridines Active on the SIRT1/AMPK Pathway Ameliorate Skin Repair and Mitochondrial Function and Exhibit Inhibition of Proliferation in Cancer Cells

(2016) Sergio Valente et al.   JOURNAL OF MEDICINAL CHEMISTRY

5-((3-Amidobenzyl)oxy)nicotinamides as Sirtuin 2 Inhibitors

(2016) Teng Ai et al.   JOURNAL OF MEDICINAL CHEMISTRY

SIRT7-dependent deacetylation of the U3-55k protein controls pre-rRNA processing

(2016) Sifan Chen et al.   Nature Communications

SIRT7 is a histone desuccinylase that functionally links to chromatin compaction and genome stability

(2016) Lei Li et al.   Nature Communications

Sirtuin functions and modulation: from chemistry to the clinic

(2016) Vincenzo Carafa et al.   Clinical Epigenetics

Sirtuins Link Inflammation and Metabolism

(2016) Vidula T. Vachharajani et al.   Journal of Immunology Research

Sirt1 activation by resveratrol is substrate sequence-selective

(2016) Mahadevan Lakshminarasimhan et al.   Aging-US

SIRT5 regulation of ammonia-induced autophagy and mitophagy

(2015) Lucia Polletta et al.   Autophagy

Protective role of SIRT5 against motor deficit and dopaminergic degeneration in MPTP-induced mice model of Parkinson's disease

(2015) Lei Liu et al.   BEHAVIOURAL BRAIN RESEARCH

Discovery of bicyclic pyrazoles as class III histone deacetylase SIRT1 and SIRT2 inhibitors

(2015) Eric Therrien et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Tumour-suppressive function of SIRT4 in human colorectal cancer

(2015) M Miyo et al.   BRITISH JOURNAL OF CANCER

An exploratory double-blind, randomized clinical trial with selisistat, a SirT1 inhibitor, in patients with Huntington's disease

(2015) Sigurd D. Süssmuth et al.   BRITISH JOURNAL OF CLINICAL PHARMACOLOGY

The Selective Sirtuin 1 Activator SRT2104 Reduces Endotoxin-Induced Cytokine Release and Coagulation Activation in Humans*

(2015) Anne J. van der Meer et al.   CRITICAL CARE MEDICINE

Sirtuin 1 promotes the growth and cisplatin resistance of endometrial carcinoma cells: a novel therapeutic target

(2015) Ryoichi Asaka et al.   LABORATORY INVESTIGATION

Sirtuin 3 regulates Foxo3a-mediated antioxidant pathway in microglia

(2015) P. Rangarajan et al.   NEUROSCIENCE

Selective Sirt2 inhibition by ligand-induced rearrangement of the active site

(2015) Tobias Rumpf et al.   Nature Communications

Crystallographic structure of a small molecule SIRT1 activator-enzyme complex

(2015) Han Dai et al.   Nature Communications

A Randomized, Placebo-Controlled Study of SRT2104, a SIRT1 Activator, in Patients with Moderate to Severe Psoriasis

(2015) James G. Krueger et al.   PLoS One

Chemical Probing of the Human Sirtuin 5 Active Site Reveals Its Substrate Acyl Specificity and Peptide-Based Inhibitors

(2014) Claudia Roessler et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Sirtuin 1 facilitates chemoresistance of pancreatic cancer cells by regulating adaptive response to chemotherapy-induced stress

(2014) Jun-gang Zhang et al.   CANCER SCIENCE

Sirtuin 4 Is a Lipoamidase Regulating Pyruvate Dehydrogenase Complex Activity

(2014) Rommel A. Mathias et al.   CELL

Lysine Glutarylation Is a Protein Posttranslational Modification Regulated by SIRT5

(2014) Minjia Tan et al.   Cell Metabolism

The Sirt1 activator SRT3025 provides atheroprotection in Apoe−/− mice by reducing hepatic Pcsk9 secretion and enhancing Ldlr expression

(2014) Melroy X. Miranda et al.   EUROPEAN HEART JOURNAL

New assays and approaches for discovery and design of Sirtuin modulators

(2014) Mike Schutkowski et al.   Expert Opinion on Drug Discovery

A potent and selective Sirtuin 1 inhibitor alleviates pathology in multiple animal and cell models of Huntington's disease

(2014) Marianne R. Smith et al.   HUMAN MOLECULAR GENETICS

Development of Pyrazolone and Isoxazol-5-one Cambinol Analogues as Sirtuin Inhibitors

(2014) Sumit S. Mahajan et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of Potent and Selective Sirtuin 2 (SIRT2) Inhibitors Using a Fragment-Based Approach

(2014) Huaqing Cui et al.   JOURNAL OF MEDICINAL CHEMISTRY

Chroman-4-one- and Chromone-Based Sirtuin 2 Inhibitors with Antiproliferative Properties in Cancer Cells

(2014) Tina Seifert et al.   JOURNAL OF MEDICINAL CHEMISTRY

SIRT5 Regulates the Mitochondrial Lysine Succinylome and Metabolic Networks

(2013) Matthew J. Rardin et al.   Cell Metabolism

Activation of the Protein Deacetylase SIRT6 by Long-chain Fatty Acids and Widespread Deacylation by Mammalian Sirtuins

(2013) Jessica L. Feldman et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Discovery of Thieno[3,2-d]pyrimidine-6-carboxamides as Potent Inhibitors of SIRT1, SIRT2, and SIRT3

(2013) Jeremy S. Disch et al.   JOURNAL OF MEDICINAL CHEMISTRY

The 2.5 Å Crystal Structure of the SIRT1 Catalytic Domain Bound to Nicotinamide Adenine Dinucleotide (NAD+) and an Indole (EX527 Analogue) Reveals a Novel Mechanism of Histone Deacetylase Inhibition

(2013) Xun Zhao et al.   JOURNAL OF MEDICINAL CHEMISTRY

The Identification of the SIRT1 Activator SRT2104 as a Clinical Candidate

(2013) Pui Ng et al.   Letters in Drug Design & Discovery

SIRT4 Coordinates the Balance between Lipid Synthesis and Catabolism by Repressing Malonyl CoA Decarboxylase

(2013) Gaëlle Laurent et al.   MOLECULAR CELL

SIRT6 regulates TNF-α secretion through hydrolysis of long-chain fatty acyl lysine

(2013) Hong Jiang et al.   NATURE

Ex-527 inhibits Sirtuins by exploiting their unique NAD+-dependent deacetylation mechanism

(2013) M. Gertz et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Evidence for a Common Mechanism of SIRT1 Regulation by Allosteric Activators

(2013) B. P. Hubbard et al.   SCIENCE

An acetylome peptide microarray reveals specificities and deacetylation substrates for all human sirtuin isoforms

(2013) David Rauh et al.   Nature Communications

Janus-faced role of SIRT1 in tumorigenesis

(2012) Na-Young Song et al.   Annals of the New York Academy of Sciences

Pharmacokinetics and tolerability of SRT2104, a first-in-class small molecule activator of SIRT1, after single and repeated oral administration in man

(2012) Ethan Hoffmann et al.   BRITISH JOURNAL OF CLINICAL PHARMACOLOGY

Sirtuin Catalysis and Regulation

(2012) Jessica L. Feldman et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Design, Synthesis, and Biological Activity of a Novel Series of Human Sirtuin-2-Selective Inhibitors

(2012) Takayoshi Suzuki et al.   JOURNAL OF MEDICINAL CHEMISTRY

Benzodeazaoxaflavins as Sirtuin Inhibitors with Antiproliferative Properties in Cancer Stem Cells

(2012) Dante Rotili et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of Salermide-Related Sirtuin Inhibitors: Binding Mode Studies and Antiproliferative Effects in Cancer Cells Including Cancer Stem Cells

(2012) Dante Rotili et al.   JOURNAL OF MEDICINAL CHEMISTRY

Synthesis and Evaluation of Substituted Chroman-4-one and Chromone Derivatives as Sirtuin 2-Selective Inhibitors

(2012) Maria Fridén-Saxin et al.   JOURNAL OF MEDICINAL CHEMISTRY

SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation

(2012) Matthew F. Barber et al.   NATURE

A Pilot Randomized, Placebo Controlled, Double Blind Phase I Trial of the Novel SIRT1 Activator SRT2104 in Elderly Volunteers

(2012) Vincenzo Libri et al.   PLoS One

The Sirtuin 2 Inhibitor AK-7 Is Neuroprotective in Huntington’s Disease Mouse Models

(2012) Vanita Chopra et al.   Cell Reports

Simplification of the tetracyclic SIRT1-selective inhibitor MC2141: Coumarin- and pyrimidine-based SIRT1/2 inhibitors with different selectivity profile

(2011) Dante Rotili et al.   BIOORGANIC & MEDICINAL CHEMISTRY

SIRT3 Opposes Reprogramming of Cancer Cell Metabolism through HIF1α Destabilization

(2011) Lydia W.S. Finley et al.   CANCER CELL

The sirtuin SIRT6 deacetylates H3 K56Ac in vivo to promote genomic stability

(2011) Bo Yang et al.   CELL CYCLE

In mammalian muscle, SIRT3 is present in mitochondria and not in the nucleus; and SIRT3 is upregulated by chronic muscle contraction in an adenosine monophosphate-activated protein kinase–independent manner

(2011) Brendon J. Gurd et al.   METABOLISM-CLINICAL AND EXPERIMENTAL

Sirt1 mediates neuroprotection from mutant huntingtin by activation of the TORC1 and CREB transcriptional pathway

(2011) Hyunkyung Jeong et al.   NATURE MEDICINE

Sirt5 Is a NAD-Dependent Protein Lysine Demalonylase and Desuccinylase

(2011) J. Du et al.   SCIENCE

Sirt3 Mediates Reduction of Oxidative Damage and Prevention of Age-Related Hearing Loss under Caloric Restriction

(2010) Shinichi Someya et al.   CELL

Identification of Tri- and Tetracyclic Pyrimidinediones as Sirtuin Inhibitors

(2010) Dante Rotili et al.   ChemMedChem

SIRT1 Activation by Small Molecules

(2010) Han Dai et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

SRT1720, SRT2183, SRT1460, and Resveratrol Are Not Direct Activators of SIRT1

(2010) Michelle Pacholec et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Biochemical characterization, localization, and tissue distribution of the longer form of mouse SIRT3

(2010) Lei Jin et al.   PROTEIN SCIENCE

Acetylation Targets Mutant Huntingtin to Autophagosomes for Degradation

(2009) Hyunkyung Jeong et al.   CELL

SIRT2-mediated protein deacetylation: An emerging key regulator in brain physiology and pathology

(2009) Kai Harting et al.   EUROPEAN JOURNAL OF CELL BIOLOGY

Novel Cambinol Analogs as Sirtuin Inhibitors: Synthesis, Biological Evaluation, and Rationalization of Activity

(2009) Federico Medda et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of Imidazo[1,2-b]thiazole Derivatives as Novel SIRT1 Activators

(2009) Chi B. Vu et al.   JOURNAL OF MEDICINAL CHEMISTRY

Study of 1,4-Dihydropyridine Structural Scaffold: Discovery of Novel Sirtuin Activators and Inhibitors

(2009) Antonello Mai et al.   JOURNAL OF MEDICINAL CHEMISTRY

Characterization of Sirtuin Inhibitors in Nematodes Expressing a Muscular Dystrophy Protein Reveals Muscle Cell and Behavioral Protection by Specific Sirtinol Analogues

(2009) Matthieu Y. Pasco et al.   JOURNAL OF MEDICINAL CHEMISTRY

Inhibition of specific HDACs and sirtuins suppresses pathogenesis in a Drosophila model of Huntington’s disease

(2008) Judit Pallos et al.   HUMAN MOLECULAR GENETICS

SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin

(2008) Eriko Michishita et al.   NATURE

Salermide, a Sirtuin inhibitor with a strong cancer-specific proapoptotic effect

(2008) E Lara et al.   ONCOGENE