Promising drug discovery strategies for sirtuin modulators: what lessons have we learnt?

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

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

Manipulating Sirtuin 3 pathway ameliorates renal damage in experimental diabetes

(2020) Monica Locatelli et al.   Scientific Reports

Curcumin induces multiple signaling pathways leading to vascular smooth muscle cell senescence

(2019) Wioleta Grabowska et al.   BIOGERONTOLOGY

Molecular basis for hierarchical histone de-β-hydroxybutyrylation by SIRT3

(2019) Xingrun Zhang et al.   Cell Discovery

Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence

(2018) Luis Rajman et al.   Cell Metabolism

Fisetin as a caloric restriction mimetic protects rat brain against aging induced oxidative stress, apoptosis and neurodegeneration

(2018) Sandeep Singh et al.   LIFE SCIENCES

Impact of curcumin on sirtuins: A review

(2018) Elham Zendedel et al.   JOURNAL OF CELLULAR BIOCHEMISTRY

The Role of SIRT3 in the Brain Under Physiological and Pathological Conditions

(2018) Elena Sidorova-Darmos et al.   Frontiers in Cellular Neuroscience

Natural polyphenols as sirtuin 6 modulators

(2018) Minna Rahnasto-Rilla et al.   Scientific Reports

Cyclic tripeptide-based potent human SIRT7 inhibitors

(2018) Shengchao Li et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

An overview of Sirtuins as potential therapeutic target: Structure, function and modulators

(2018) Yijie Wang et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Structural Basis of Sirtuin 6 Inhibition by the Hydroxamate Trichostatin A: Implications for Protein Deacylase Drug Development

(2018) Weijie You et al.   JOURNAL OF MEDICINAL CHEMISTRY

SIRT7-Dependent Deacetylation of Fibrillarin Controls Histone H2A Methylation and rRNA Synthesis during the Cell Cycle

(2018) Aishwarya Iyer-Bierhoff et al.   Cell Reports

Metformin Is a Direct SIRT1-Activating Compound: Computational Modeling and Experimental Validation

(2018) Elisabet Cuyàs et al.   Frontiers in Endocrinology

Luteolinidin Protects the Postischemic Heart through CD38 Inhibition with Preservation of NAD(P)(H)

(2017) James Boslett et al.   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

Luteolin and fisetin suppress oxidative stress by modulating sirtuins and forkhead box O3a expression under in vitro diabetic conditions

(2017) Arang Kim et al.   Nutrition Research and Practice

Honokiol, an activator of Sirtuin-3 (SIRT3) preserves mitochondria and protects the heart from doxorubicin-induced cardiomyopathy in mice

(2017) Vinodkumar B. Pillai et al.   Oncotarget

Low-dose suramin in autism spectrum disorder: a small, phase I/II, randomized clinical trial

(2017) Robert K. Naviaux et al.   Annals of Clinical and Translational Neurology

Structural Basis of Sirtuin 6 Activation by Synthetic Small Molecules

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

Curcumin pretreatment attenuates inflammation and mitochondrial dysfunction in experimental stroke: The possible role of Sirt1 signaling

(2016) Yanping Miao et al.   BRAIN RESEARCH BULLETIN

NAD + Replenishment Improves Lifespan and Healthspan in Ataxia Telangiectasia Models via Mitophagy and DNA Repair

(2016) Evandro Fei Fang et al.   Cell Metabolism

Aging-related 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurochemial and behavioral deficits and redox dysfunction: improvement by AK-7

(2016) Qiang Guan et al.   EXPERIMENTAL GERONTOLOGY

High-throughput screening of Sirtuin family of genes in breast cancer

(2016) Mehri Igci et al.   GENE

Activation of the AMPK/Sirt1 pathway by a leucine–metformin combination increases insulin sensitivity in skeletal muscle, and stimulates glucose and lipid metabolism and increases life span in Caenorhabditis elegans

(2016) Jheelam Banerjee et al.   METABOLISM-CLINICAL AND EXPERIMENTAL

PGC1α drives NAD biosynthesis linking oxidative metabolism to renal protection

(2016) Mei T. Tran et al.   NATURE

Slowing ageing by design: the rise of NAD+ and sirtuin-activating compounds

(2016) Michael S. Bonkowski et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

DNA repair targeted therapy: The past or future of cancer treatment?

(2016) Navnath S. Gavande et al.   PHARMACOLOGY & THERAPEUTICS

The SIRT2 Deacetylase Stabilizes Slug to Control Malignancy of Basal-like Breast Cancer

(2016) Wenhui Zhou et al.   Cell Reports

Diet and exercise signals regulate SIRT3 and activate AMPK and PGC-1α in skeletal muscle

(2016) Orsolya M. Palacios et al.   Aging-US

A SIRT4-like auto ADP-ribosyltransferase is essential for the environmental growth ofMycobacterium smegmatis

(2015) Yongcong Tan et al.   ACTA BIOCHIMICA ET BIOPHYSICA SINICA

The role of sirtuins in cardiac disease

(2015) Shouji Matsushima et al.   AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY

Mitochondrial Sirtuins and Their Relationships with Metabolic Disease and Cancer

(2015) Surinder Kumar et al.   ANTIOXIDANTS & REDOX SIGNALING

Fisetin induces Sirt1 expression while inhibiting early adipogenesis in 3T3-L1 cells

(2015) Sang Chon Kim et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

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

AK-1, a specific SIRT2 inhibitor, induces cell cycle arrest by downregulating Snail in HCT116 human colon carcinoma cells

(2015) Min Gyeong Cheon et al.   CANCER LETTERS

The complex role of SIRT6 in carcinogenesis

(2015) Batia Lerrer et al.   CARCINOGENESIS

SIRT3 Is Crucial for Maintaining Skeletal Muscle Insulin Action and Protects Against Severe Insulin Resistance in High-Fat–Fed Mice

(2015) Louise Lantier et al.   DIABETES

Polymorphisms Falling Within Putative miRNA Target Sites in the 3′UTR Region ofSIRT2andDRD2Genes Are Correlated With Human Longevity

(2015) Paolina Crocco et al.   JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES

A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease

(2015) R. Scott Turner et al.   NEUROLOGY

Emerging Role of Sirtuin 2 in the Regulation of Mammalian Metabolism

(2015) Pedro Gomes et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Differential expression of sirtuins in the aging rat brain

(2015) Nady Braidy et al.   Frontiers in Cellular Neuroscience

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

(2015) Tobias Rumpf et al.   Nature Communications

Honokiol blocks and reverses cardiac hypertrophy in mice by activating mitochondrial Sirt3

(2015) Vinodkumar B. Pillai et al.   Nature Communications

Curcumin as therapeutics for the treatment of head and neck squamous cell carcinoma by activating SIRT1

(2015) An Hu et al.   Scientific Reports

Huntington disease

(2015) Gillian P. Bates et al.   Nature Reviews Disease Primers

SRT2104 extends survival of male mice on a standard diet and preserves bone and muscle mass

(2014) Evi M. Mercken et al.   AGING CELL

Activation of SIRT1 by curcumin blocks the neurotoxicity of amyloid-β25–35 in rat cortical neurons

(2014) Qinru Sun et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Chromone: A Valid Scaffold in Medicinal Chemistry

(2014) Alexandra Gaspar et al.   CHEMICAL REVIEWS

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

Sirtuin inhibitors as anticancer agents

(2014) Jing Hu et al.   Future Medicinal Chemistry

Modulation of human longevity by SIRT3 single nucleotide polymorphisms in the prospective study “Treviso Longeva (TRELONG)”

(2013) Diego Albani et al.   AGE

SirT1 Regulation of Antioxidant Genes Is Dependent on the Formation of a FoxO3a/PGC-1α Complex

(2013) Yolanda Olmos et al.   ANTIOXIDANTS & REDOX SIGNALING

SIRT5 desuccinylates and activates SOD1 to eliminate ROS

(2013) Zhi-Feng Lin et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Growth hormone and melatonin prevent age-related alteration in apoptosis processes in the dentate gyrus of male rats

(2013) R. A. Kireev et al.   BIOGERONTOLOGY

Caloric restriction and its mimetics

(2013) Shin-Hae Lee et al.   BMB Reports

SIRT1 and SIRT2: emerging targets in neurodegeneration

(2013) Gizem Donmez et al.   EMBO Molecular Medicine

SIRT1 activation by curcumin pretreatment attenuates mitochondrial oxidative damage induced by myocardial ischemia reperfusion injury

(2013) Yang Yang et al.   FREE RADICAL BIOLOGY AND MEDICINE

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

Vitexin Inhibits Inflammatory Pain in Mice by Targeting TRPV1, Oxidative Stress, and Cytokines

(2013) Sergio M. Borghi et al.   JOURNAL OF NATURAL PRODUCTS

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

A small molecule Inauhzin inhibits SIRT1 activity and suppresses tumour growth through activation of p53

(2012) Qi Zhang et al.   EMBO Molecular Medicine

Can targeting SIRT-1 to treat type 2 diabetes be a good strategy? A review

(2012) Venkat Koushik Pulla et al.   EXPERT OPINION ON THERAPEUTIC TARGETS

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

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

Emerging roles of SIRT6 on telomere maintenance, DNA repair, metabolism and mammalian aging

(2012) Gaoxiang Jia et al.   MOLECULAR AND CELLULAR BIOCHEMISTRY

The sirtuin SIRT6 regulates lifespan in male mice

(2012) Yariv Kanfi et al.   NATURE

The sirtuin SIRT6 blocks IGF-Akt signaling and development of cardiac hypertrophy by targeting c-Jun

(2012) Nagalingam R Sundaresan et al.   NATURE MEDICINE

A Molecular Mechanism for Direct Sirtuin Activation by Resveratrol

(2012) Melanie Gertz et al.   PLoS One

AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network

(2011) Antero Salminen et al.   AGEING RESEARCH REVIEWS

Flavonoids as inhibitors of human CD38

(2011) Esther Kellenberger et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

The Sirtuin 2 microtubule deacetylase is an abundant neuronal protein that accumulates in the aging CNS

(2011) Michele M. Maxwell et al.   HUMAN MOLECULAR GENETICS

AMP-activated protein kinase inhibits NF-κB signaling and inflammation: impact on healthspan and lifespan

(2011) Antero Salminen et al.   JOURNAL OF MOLECULAR MEDICINE-JMM

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

(2011) Hyunkyung Jeong et al.   NATURE MEDICINE

Resveratrol-Activated AMPK/SIRT1/Autophagy in Cellular Models of Parkinson’s Disease

(2011) Yuncheng Wu et al.   NEUROSIGNALS

The Deacetylase SIRT1 Promotes Membrane Localization and Activation of Akt and PDK1 During Tumorigenesis and Cardiac Hypertrophy

(2011) N. R. Sundaresan et al.   Science Signaling

Mammalian Sirtuins: Biological Insights and Disease Relevance

(2010) Marcia C. Haigis et al.   Annual Review of Pathology-Mechanisms of Disease

Regulation of SIRT1 in cellular functions: Role of polyphenols

(2010) Sangwoon Chung et al.   ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS

SIRT3 Is a Mitochondria-Localized Tumor Suppressor Required for Maintenance of Mitochondrial Integrity and Metabolism during Stress

(2010) Hyun-Seok Kim et al.   CANCER CELL

Silent Information Regulator 1 Protects the Heart From Ischemia/Reperfusion

(2010) Chiao-Po Hsu et al.   CIRCULATION

Induction of Hypothalamic Sirt1 Leads to Cessation of Feeding via Agouti-Related Peptide

(2010) Tsutomu Sasaki et al.   ENDOCRINOLOGY

Distinct regulation of mitochondrial localization and stability of two human Sirt5 isoforms

(2010) Nobuko Matsushita et al.   GENES TO CELLS

SIRT4 Regulates Fatty Acid Oxidation and Mitochondrial Gene Expression in Liver and Muscle Cells

(2010) Nargis Nasrin et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

SIRT Inhibitors Induce Cell Death and p53 Acetylation through Targeting Both SIRT1 and SIRT2

(2010) Barrie Peck et al.   MOLECULAR CANCER THERAPEUTICS

Genomic instability — an evolving hallmark of cancer

(2010) Simona Negrini et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Ten years of NAD-dependent SIR2 family deacetylases: implications for metabolic diseases

(2010) Shin-ichiro Imai et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Quercetin increases brain and muscle mitochondrial biogenesis and exercise tolerance

(2009) J. Mark Davis et al.   AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY

Identification of a small molecule SIRT2 inhibitor with selective tumor cytotoxicity

(2009) Yingjia Zhang et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Sirtuins inhibitors: The approach to affinity and selectivity

(2009) Yana Cen   BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS

SIRT5 Deacetylates Carbamoyl Phosphate Synthetase 1 and Regulates the Urea Cycle

(2009) Takashi Nakagawa et al.   CELL

Human longevity and 11p15.5: a study in 1321 centenarians

(2009) Francesco Lescai et al.   EUROPEAN JOURNAL OF HUMAN GENETICS

Novel 3-Arylideneindolin-2-ones as Inhibitors of NAD+-Dependent Histone Deacetylases (Sirtuins)

(2009) Kilian Huber et al.   JOURNAL OF MEDICINAL CHEMISTRY

The SIRT1 activator resveratrol protects SK-N-BE cells from oxidative stress and against toxicity caused by α-synuclein or amyloid-β (1-42) peptide

(2009) Diego Albani et al.   JOURNAL OF NEUROCHEMISTRY

AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity

(2009) Carles Cantó et al.   NATURE

SIRT1 and insulin resistance

(2009) Fengxia Liang et al.   Nature Reviews Endocrinology

High Histone Deacetylase 7 (HDAC7) Expression Is Significantly Associated with Adenocarcinomas of the Pancreas

(2008) Mehdi Ouaïssi et al.   ANNALS OF SURGICAL ONCOLOGY

Discovery, In Vivo Activity, and Mechanism of Action of a Small-Molecule p53 Activator

(2008) Sonia Lain et al.   CANCER CELL

Impaired DNA Damage Response, Genome Instability, and Tumorigenesis in SIRT1 Mutant Mice

(2008) Rui-Hong Wang et al.   CANCER CELL

The NAD+-Dependent Deacetylase SIRT1 Modulates CLOCK-Mediated Chromatin Remodeling and Circadian Control

(2008) Yasukazu Nakahata et al.   CELL

Sirt7 Increases Stress Resistance of Cardiomyocytes and Prevents Apoptosis and Inflammatory Cardiomyopathy in Mice

(2008) Olesya Vakhrusheva et al.   CIRCULATION RESEARCH

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

(2008) Judit Pallos et al.   HUMAN MOLECULAR GENETICS

SIRT1 Modulation of the Acetylation Status, Cytosolic Localization, and Activity of LKB1

(2008) Fan Lan et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Structure–Activity Studies on Splitomicin Derivatives as Sirtuin Inhibitors and Computational Prediction of Binding Mode

(2008) Robert C. Neugebauer et al.   JOURNAL OF MEDICINAL CHEMISTRY

Brain SIRT1: Anatomical Distribution and Regulation by Energy Availability

(2008) G. Ramadori et al.   JOURNAL OF NEUROSCIENCE

SIRT3 Is a Stress-Responsive Deacetylase in Cardiomyocytes That Protects Cells from Stress-Mediated Cell Death by Deacetylation of Ku70

(2008) N. R. Sundaresan et al.   MOLECULAR AND CELLULAR BIOLOGY

A fasting inducible switch modulates gluconeogenesis via activator/coactivator exchange

(2008) Yi Liu et al.   NATURE

Paths of Convergence: Sirtuins in Aging and Neurodegeneration

(2008) Li Gan et al.   NEURON

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

(2008) E Lara et al.   ONCOGENE

The SIRT1 Deacetylase Suppresses Intestinal Tumorigenesis and Colon Cancer Growth

(2008) Ron Firestein et al.   PLoS One