sirtuin 1 | 3.5.1.- Histone deacetylases (HDACs) | IUPHAR Guide to IMMUNOPHARMACOLOGY

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sirtuin 1

Target id: 2707

Nomenclature: sirtuin 1

Family: 3.5.1.- Histone deacetylases (HDACs)

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: ON :     sirtuin 1 has curated data in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 747 10q21 SIRT1 sirtuin 1
Mouse - 737 10 B4 Sirt1 sirtuin 1
Rat - - 20p11 Sirt1 sirtuin 1
Database Links
CATH/Gene3D
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia

Download all structure-activity data for this target as a CSV file

Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
SRT1720 Hs Activation 6.8 pEC50 3
pEC50 6.8 (EC50 1.6x10-7 M) [3]
SIRT1 activator 3 Hs Activation >6.0 pIC50 4
pIC50 >6.0 (IC50 <1x10-6 M) [4]
Description: In an enzymatic assay
SRT2104 Hs Activation - - 5
EC1.5 is 430nM. [5]
Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
compound 17 [PMID: 23570514] Hs Inhibition 8.2 pIC50 2
pIC50 8.2 (IC50 6.7x10-9 M) [2]
selisistat Hs Inhibition 7.4 pIC50 8
pIC50 7.4 (IC50 3.8x10-8 M) [8]
splitomicin Hs Inhibition 4.0 pIC50 6
pIC50 4.0 (IC50 9.62x10-5 M) [6]
Physiological Functions
Sirt1 induces inflammatory signaling in response to environmental stress.
Species:  Mouse
Tissue:  Macrophages in liver and adipose tissue.
References:  7
Sirt1 modulates the acetylation status of the RelA/p65 subunit of NF-κB critically contributing towards regulation of the inflammatory, immune, and apoptotic responses in mammals.
Species:  Mouse
Tissue:  Macrophages
References:  7
Physiological Consequences of Altering Gene Expression
Myeloid cell–specific Sirt1 knockout mice exhibit increased inflammatory responses and susceptibility to Mycobacterium tuberculosis infection.
Species:  Human
Tissue:  Myeloid cells, lung tissue.
Technique:  Cre-Lox-driven recombination.
References:  1

References

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1. Cheng CY, Gutierrez NM, Marzuki MB, Lu X, Foreman TW, Paleja B, Lee B, Balachander A, Chen J, Kurepina N et al.. (2017) Host sirtuin 1 regulates mycobacterial immunopathogenesis and represents a therapeutic target against tuberculosis. Science Immunology, 2 (9) Online ahead of print.

2. Disch JS, Evindar G, Chiu CH, Blum CA, Dai H, Jin L, Schuman E, Lind KE, Belyanskaya SL, Deng J et al.. (2013) Discovery of thieno[3,2-d]pyrimidine-6-carboxamides as potent inhibitors of SIRT1, SIRT2, and SIRT3. J. Med. Chem., 56 (9): 3666-79. [PMID:23570514]

3. Milne JC, Lambert PD, Schenk S, Carney DP, Smith JJ, Gagne DJ, Jin L, Boss O, Perni RB, Vu CB et al.. (2007) Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature, 450 (7170): 712-6. [PMID:18046409]

4. Nayagam VM, Wang X, Tan YC, Poulsen A, Goh KC, Ng T, Wang H, Song HY, Ni B, Entzeroth M et al.. (2006) SIRT1 modulating compounds from high-throughput screening as anti-inflammatory and insulin-sensitizing agents. J Biomol Screen, 11 (8): 959-67. [PMID:17099246]

5. Ng PY, Bemis JE, Disch JS, Vu CB, Oalmann CJ, Lynch AV, Carney DP, Riera TV, Song J, Smith JJ et al.. (2013) The Identification of the SIRT1 Activator SRT2104 as a Clinical Candidate. Letters in Drug Design & Discovery, 10: 793-797.

6. Pasco MY, Rotili D, Altucci L, Farina F, Rouleau GA, Mai A, Néri C. (2010) Characterization of sirtuin inhibitors in nematodes expressing a muscular dystrophy protein reveals muscle cell and behavioral protection by specific sirtinol analogues. J. Med. Chem., 53 (3): 1407-11. [PMID:20041717]

7. Schug TT, Xu Q, Gao H, Peres-da-Silva A, Draper DW, Fessler MB, Purushotham A, Li X. (2010) Myeloid deletion of SIRT1 induces inflammatory signaling in response to environmental stress. Mol. Cell. Biol., 30 (19): 4712-21. [PMID:20647536]

8. Solomon JM, Pasupuleti R, Xu L, McDonagh T, Curtis R, DiStefano PS, Huber LJ. (2006) Inhibition of SIRT1 catalytic activity increases p53 acetylation but does not alter cell survival following DNA damage. Mol. Cell. Biol., 26 (1): 28-38. [PMID:16354677]

How to cite this page

3.5.1.- Histone deacetylases (HDACs): sirtuin 1. Last modified on 18/07/2017. Accessed on 18/01/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2707.