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sirtuin 1

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 2707

Nomenclature: sirtuin 1

Family: 3.5.1.- Histone deacetylases (HDACs)

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 747 10q21.3 SIRT1 sirtuin 1
Mouse - 737 10 B4 Sirt1 sirtuin 1
Rat - - 20p11 Sirt1 sirtuin 1
Database Links Click here for help
Alphafold Q96EB6 (Hs), Q923E4 (Mm)
CATH/Gene3D 3.40.50.1220
ChEMBL Target CHEMBL4506 (Hs)
Ensembl Gene ENSG00000096717 (Hs), ENSMUSG00000020063 (Mm), ENSRNOG00000051592 (Rn)
Entrez Gene 23411 (Hs), 93759 (Mm), 309757 (Rn)
Human Protein Atlas ENSG00000096717 (Hs)
KEGG Gene hsa:23411 (Hs), mmu:93759 (Mm), rno:309757 (Rn)
OMIM 604479 (Hs)
Pharos Q96EB6 (Hs)
RefSeq Nucleotide NM_012238 (Hs), NM_019812 (Mm)
RefSeq Protein NP_036370 (Hs), NP_062786 (Mm)
UniProtKB Q96EB6 (Hs), Q923E4 (Mm)
Wikipedia SIRT1 (Hs)

Download all structure-activity data for this target as a CSV file go icon to follow link

Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
SRT1720 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Immunopharmacology Ligand Hs Activation 6.8 pEC50 3
⤷ pEC50 6.8 (EC50 1.6x10-7 M) [3]
SIRT1 activator 3 Small molecule or natural product Immunopharmacology Ligand Hs Activation >6.0 pIC50 4
⤷ pIC50 >6.0 (IC50 <1x10-6 M) [4]
Description: In an enzymatic assay
SRT2104 Small molecule or natural product Immunopharmacology Ligand 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 Value Parameter Reference
compound 17 [PMID: 23570514] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.2 pIC50 2
⤷ pIC50 8.2 (IC50 6.7x10-9 M) [2]
selisistat Small molecule or natural product Primary target of this compound Hs Inhibition 7.4 pIC50 8
⤷ pIC50 7.4 (IC50 3.8x10-8 M) [8]
splitomicin Small molecule or natural product Hs Inhibition 4.0 pIC50 6
⤷ pIC50 4.0 (IC50 9.62x10-5 M) [6]
Immunopharmacology Comments
Sirtuin 1 has been suggested as a molecular target for host-directed therapy against Mycobacterium tuberculosis infection by research that shows that activation of sirtuin 1 decreases lung pathology, reduces inflammation, and enhances drug efficacy against Mycobacterium tuberculosis [1].
Immuno Process Associations
Immuno Process:  T cell (activation)
Immuno Process:  B cell (activation)
Immuno Process:  Immune regulation
Immuno Process:  Immune system development
Immuno Process:  Cytokine production & signalling
Immuno Process:  Cellular signalling
Physiological Functions Click here for help
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 Click here for help
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, Tsenova L et al.. (2017) Host sirtuin 1 regulates mycobacterial immunopathogenesis and represents a therapeutic target against tuberculosis. Sci Immunol, 2 (9). [PMID:28707004]

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. Lett Drug Des Discov, 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 18/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2707.