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sirtuin 2

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Target id: 2708

Nomenclature: sirtuin 2

Family: 3.5.1.- Histone deacetylases (HDACs)

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 389 19q13.2 SIRT2 sirtuin 2
Mouse - 389 7 B1 Sirt2 sirtuin 2
Rat - 350 1q21 Sirt2 sirtuin 2
Database Links Click here for help
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
RefSeq Nucleotide
RefSeq Protein
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Human SIRT2 histone deacetylase
PDB Id:  1J8F
Resolution:  1.7Å
Species:  Human
References:  4
Enzyme Reaction Click here for help
EC Number: 3.5.1.-

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

Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound 86 [PMID: 26982234] Small molecule or natural product Primary target of this compound Hs Inhibition 7.1 pKi 1
pKi 7.1 (Ki 7.3x10-8 M) [1]
compound 17 [PMID: 23570514] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.7 pIC50 3
pIC50 8.7 (IC50 1.8x10-9 M) [3]
AGK2 Small molecule or natural product Hs Inhibition 4.5 – 5.8 pIC50 2,6
pIC50 4.5 – 5.8 (IC50 3.5x10-5 – 1.56x10-6 M) [2,6]
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Antigen presentation
General Comments
SIRT2 is NAD+-dependent protein deacetylase, which deacetylates internal lysines on histone, α-tubulin and some transcription factors. SIRT2 is the most abundant sirtuin in the brain [7]. Selective pharmacological blockade of SIRT2 is being investigated for potential clinical benefit in neurodegenerative diseases (and cancers [5]), with initial research focussing on the synucleinopathy, Parkinson's disease [6].


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1. Ai T, Wilson DJ, More SS, Xie J, Chen L. (2016) 5-((3-Amidobenzyl)oxy)nicotinamides as Sirtuin 2 Inhibitors. J Med Chem, 59 (7): 2928-41. [PMID:26982234]

2. Cui H, Kamal Z, Ai T, Xu Y, More SS, Wilson DJ, Chen L. (2014) Discovery of potent and selective sirtuin 2 (SIRT2) inhibitors using a fragment-based approach. J Med Chem, 57 (20): 8340-57. [PMID:25275824]

3. 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]

4. Finnin MS, Donigian JR, Pavletich NP. (2001) Structure of the histone deacetylase SIRT2. Nat Struct Biol, 8 (7): 621-5. [PMID:11427894]

5. Hu J, Jing H, Lin H. (2014) Sirtuin inhibitors as anticancer agents. Future Med Chem, 6 (8): 945-66. [PMID:24962284]

6. Outeiro TF, Kontopoulos E, Altmann SM, Kufareva I, Strathearn KE, Amore AM, Volk CB, Maxwell MM, Rochet JC, McLean PJ et al.. (2007) Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease. Science, 317 (5837): 516-9. [PMID:17588900]

7. Pandithage R, Lilischkis R, Harting K, Wolf A, Jedamzik B, Lüscher-Firzlaff J, Vervoorts J, Lasonder E, Kremmer E, Knöll B et al.. (2008) The regulation of SIRT2 function by cyclin-dependent kinases affects cell motility. J Cell Biol, 180 (5): 915-29. [PMID:18332217]

How to cite this page

3.5.1.- Histone deacetylases (HDACs): sirtuin 2. Last modified on 14/07/2016. Accessed on 25/07/2024. IUPHAR/BPS Guide to PHARMACOLOGY,