SIRT2
SIRT2 is an NAD+-dependent sirtuin deacetylase with a catalytic core containing a Rossmann-fold NAD-binding domain and a zinc-binding module[1]. It functions as a cytoplasmic microtubule regulator by deacetylating α-tubulin Lys40 in vitro and in vivo, while SIRT2 knockdown causes tubulin hyperacetylation[2]. Mechanistically, SIRT2 also enters chromatin-linked cell-cycle control, because it deacetylates histone H4K16 during G2/M and supports mitotic chromatin regulation[3]. In cancer-relevant models, SIRT2 maintains genome integrity by deacetylating APC/C coactivators CDH1 and CDC20, and Sirt2 deficiency causes centrosome amplification, aneuploidy, and tumorigenesis in mice[4]. In neurodegeneration models, SIRT2 inhibition rescues α-synuclein toxicity and modifies inclusion morphology in cellular Parkinson’s disease models[5]. Compared with related sirtuin isoforms, SIRT2 shows distinctive cytoplasmic localization but undergoes active nuclear import controlled by its C-terminus and importins[6]. Isoform-level analysis is important because catalytically inactive nuclear SIRT2.5 antagonizes SIRT2.1 and SIRT2.2 effects on HBV replication from cccDNA[7]. For experimental applications, SIRT2 inhibitors support studies of microtubule acetylation, mitotic regulation, α-synuclein toxicity, viral chromatin control, and Myc-driven cancer signaling[2][4][5][7][8].
References:
- [1]. Finnin MS, et al. Structure of the histone deacetylase SIRT2. Nat Struct Biol. 2001 Jul;8(7):621-5. [Content Brief]
- [2]. North BJ, et al. The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase. Mol Cell. 2003 Feb;11(2):437-44. [Content Brief]
- [3]. Vaquero A, et al. SirT2 is a histone deacetylase with preference for histone H4 Lys 16 during mitosis. Genes Dev. 2006 May 15;20(10):1256-61. [Content Brief]
- [4]. Kim HS, et al. SIRT2 maintains genome integrity and suppresses tumorigenesis through regulating APC/C activity. Cancer Cell. 2011 Oct 18;20(4):487-99. [Content Brief]
- [5]. Outeiro TF, et al. Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease. Science. 2007 Jul 27;317(5837):516-9. [Content Brief]
- [6]. Eldridge MJG, et al. Active nuclear import of the deacetylase Sirtuin-2 is controlled by its C-terminus and importins. Sci Rep. 2020 Feb 10;10(1):2034. [Content Brief]
- [7]. Piracha ZZ, et al. An Alternatively Spliced Sirtuin 2 Isoform 5 Inhibits Hepatitis B Virus Replication from cccDNA by Repressing Epigenetic Modifications Made by Histone Lysine Methyltransferases. J Virol. 2020 Jul 30;94(16):e00926-20. [Content Brief]
- [8]. Brady JJ, et al. An Arntl2-Driven Secretome Enables Lung Adenocarcinoma Metastatic Self-Sufficiency. Cancer Cell. 2016 May 9;29(5):697-710. [Content Brief]
-
SIRT2 Related Products (64)
Related Products (64)
-
Antibodies (1)
-
Nicotinamide
0 ImagesNicotinamide is a form of vitamin B3 or niacin. Nicotinamide Hydrochloride inhibits SIRT2 activity (IC50: 2 μM). Nicotinamide also inhibits SIRT1. Nicotinamide increases cellular NAD+, ATP, ROS levels. Nicotinamide inhibits tumor growth and improves survival. Nicotinamide also has anti-HBV activity.
-
Suramin sodium salt
0 ImagesSuramin sodium salt (Suramin hexasodium salt) is a reversible and competitive protein-tyrosine phosphatases (PTPases) inhibitor. Suramin sodium salt is a potent inhibitor of sirtuins: SirT1 (IC50=297 nM), SirT2 (IC50=1.15 μM), and SirT5 (IC50=22 μM). Suramin sodium salt is a competitive inhibitor of reverse transcriptase (DNA topoisomerase II: IC50=5 μM). Suramin sodium salt is a potent SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) inhibitor. Suramin sodium salt efficiently inhibits IP5K and is an antiparasitic, anti-neoplastic and anti-angiogenic agent.
-
Nicotinamide (Standard)
0 ImagesSynonyms: Niacinamide(Standard); Nicotinic acid amide (Standard)Nicotinamide (Standard) is the analytical standard of Nicotinamide. This product is intended for research and analytical applications. Nicotinamide is a form of vitamin B3 or niacin. Nicotinamide Hydrochloride inhibits SIRT2 activity (IC50: 2 μM). Nicotinamide also inhibits SIRT1. Nicotinamide increases cellular NAD+, ATP, ROS levels. Nicotinamide inhibits tumor growth and improves survival. Nicotinamide also has anti-HBV activity.
-
SirReal2
0 ImagesSirReal2 is a potent, isotype-selective Sirt2 inhibitor with an IC50 value of 140 nM and has very little effect on the activities of Sirt3-5. SirReal2 leads to tubulin hyperacetylation in HeLa cells and induces destabilization of the checkpoint protein BubR1. SirReal2 combined with VS-5584 (HY-16585) suppresses tumor growth and extends the survival rate of mice in tumor xenograft model. SirReal2 is is promising for research of cancer, inflammation and neurodegeneration.
-
Tenovin-6
0 ImagesTenovin-6, an analog of Tenovin-1 (HY-13423), is an activator of p53 transcriptional activity. Tenovin-6 inhibits the protein deacetylase activities of purified human SIRT1, SIRT2, and SIRT3 with IC50s of 21 μM, 10 μM, and 67 μM, respectively. Tenovin-6 also inhibits dihydroorotate dehydrogenase (DHODH).
-
SIRT-IN-2
0 ImagesCat. No.: HY-16616CAS No.: 1431411-66-3SIRT-IN-2 is a potent inhibitor of SIRT1/2/3, with IC50s of 4, 4, 7 nM, respectively.
-
PROTAC Sirt2 Degrader-1
0 ImagesPROTAC Sirt2 Degrader-1 is a SirReal-based PROTAC, acts as a Sirt2 degrader, composed of a highly potent and isotype-selective Sirt2 inhibitor, a linker, and a bona fide Cereblon ligand for E3 ubiquitin ligase. PROTAC Sirt2 Degrader-1 shows an IC50 of 0.25 μM for Sirt2, with no effect on Sirt1/Sirt3 (IC50s>100 μM).
-
SIRT6-IN-6
0 ImagesSIRT6-IN-6 (compound 6d) is a potent and selective SIRT6 inhibitor with an IC50 of 4.93 μM and a Ki of ~10 μM. SIRT6-IN-6 shows selectivity against other members of the HDAC family (SIRT1-3 and HDAC1-11). SIRT6-IN-6 significantly increases the level of glucose transporter GLUT-1, thereby reducing blood glucose in a mouse model of type 2 diabetes. SIRT6-IN-6 can be used for type 2 diabetes research.
