Abstract
We have identified SRT2104 (4) as the first direct synthetic SIRT1 activator clinical candidate. The compound was derived from the optimization of a previously described imidazo[1,2-b]thiazole scaffold. SRT2104 was selected as a development candidate based on a combination of biochemical activity and pharmacokinetic profile. The in vivo characteristics of SRT2104 were superior to those of analogues with similar activation profiles. The overall preclinical profile suggests that the compound has potential to provide therapeutic benefit in a clinical setting.
Keywords: Activator, Imidazothiazole, SIRT1, Sirtuin, SRT1720, SRT2104.
Letters in Drug Design & Discovery
Title:The Identification of the SIRT1 Activator SRT2104 as a Clinical Candidate
Volume: 10 Issue: 9
Author(s): Meghan Duncan, Robert B. Perni, James L. Ellis, George P. Vlasuk, Michael R. Jirousek, Joseph J. Nunes, Jill C. Milne, Peter J. Elliot, Vipin Suri, Akanksha Gupta, Kristina Kriksciukaite, Marie Yeager, Pui Yee Ng, Angela Tornblom, Siva Lavu, Jesse J. Smith, Jeffrey Song, Thomas V. Riera, David P. Carney, Amy V. Lynch, Christopher J. Oalmann, Chi B. Vu, Jeremy S. Disch and Jean E. Bemis
Affiliation:
Keywords: Activator, Imidazothiazole, SIRT1, Sirtuin, SRT1720, SRT2104.
Abstract: We have identified SRT2104 (4) as the first direct synthetic SIRT1 activator clinical candidate. The compound was derived from the optimization of a previously described imidazo[1,2-b]thiazole scaffold. SRT2104 was selected as a development candidate based on a combination of biochemical activity and pharmacokinetic profile. The in vivo characteristics of SRT2104 were superior to those of analogues with similar activation profiles. The overall preclinical profile suggests that the compound has potential to provide therapeutic benefit in a clinical setting.
Export Options
About this article
Cite this article as:
Duncan Meghan, Perni B. Robert, Ellis L. James, Vlasuk P. George, Jirousek R. Michael, Nunes J. Joseph, Milne C. Jill, Elliot J. Peter, Suri Vipin, Gupta Akanksha, Kriksciukaite Kristina, Yeager Marie, Ng Yee Pui, Tornblom Angela, Lavu Siva, Smith J. Jesse, Song Jeffrey, Riera V. Thomas, Carney P. David, Lynch V. Amy, Oalmann J. Christopher, Vu B. Chi, Disch S. Jeremy and Bemis E. Jean, The Identification of the SIRT1 Activator SRT2104 as a Clinical Candidate, Letters in Drug Design & Discovery 2013; 10 (9) . https://dx.doi.org/10.2174/15701808113100990021
DOI https://dx.doi.org/10.2174/15701808113100990021 |
Print ISSN 1570-1808 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-628X |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Antiviral Properties of Quinolone-based Drugs
Current Drug Targets - Infectious Disorders Genetic Vaccination for the Immunotherapy of B-Cell Malignancies
Current Gene Therapy Immune System, Cell Senescence, Aging and Longevity - Inflamm-Aging Reappraised
Current Pharmaceutical Design Natural Aristolochia Alkaloid Aristololactam-β-D-glucoside: Interaction with Biomacromolecules and Correlation to the Biological Perspectives
Mini-Reviews in Medicinal Chemistry Analysis of Nickel-Binding Peptides in a Human Hepidermoid Cancer Cell Line by Ni-NTA Affinity Chromatography and Mass Spectrometry
Protein & Peptide Letters TNF-α Polymorphisms and Maternal Depression in a Mexican Mestizo Population
CNS & Neurological Disorders - Drug Targets GADD45 Proteins: Central Players in Tumorigenesis
Current Molecular Medicine Therapeutic Angiogenesis by Gene Therapy for Critical Limb Ischemia: Choice of Biological Agent
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Activin and TGF-β Effects on Brain Development and Neural Stem Cells
CNS & Neurological Disorders - Drug Targets The Battle of the Sexes for Stroke Therapy: Female- Versus Male-Derived Stem Cells
CNS & Neurological Disorders - Drug Targets Vitamin D in COPD - A Pleiotropic Micronutrient in a Multisystem Disease
Current Respiratory Medicine Reviews Functional Selectivity in GPCR Signaling: Understanding the Full Spectrum of Receptor Conformations
Mini-Reviews in Medicinal Chemistry Chemical Modifications of Synthetic RNAi Agents and in vivo Delivery Techniques
Current Bioactive Compounds Roles of Glycans and Glycopeptides in Immune System and Immune-Related Diseases
Current Medicinal Chemistry Soluble Epoxide Hydrolase, a Target with Multiple Opportunities for Cardiovascular Drug Discovery
Current Topics in Medicinal Chemistry Brown Recluse Spider Venom: Proteomic Analysis and Proposal of a Putative Mechanism of Action
Protein & Peptide Letters Curcumin: Structure-Activity Relationship Towards its Role as a Versatile Multi-Targeted Therapeutics
Mini-Reviews in Organic Chemistry Clinical Development of MET Targeted Therapy For Human Cancer
Current Cancer Therapy Reviews The Dual Role of Interleukin-25 in the Control of Immune-Mediated Pathologies
Current Molecular Medicine Impact of Heavy Metals on Host Cells: Special Focus on Nickel-Mediated Pathologies and Novel Interventional Approaches
Endocrine, Metabolic & Immune Disorders - Drug Targets