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]
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SIRT2 Related Products (64)
Related Products (64)
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Antibodies (1)
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Tenovin-6 Hydrochloride
0 ImagesTenovin-6 Hydrochloride, an analog of Tenovin-1 (HY-13423), is an activator of p53 transcriptional activity. Tenovin-6 Hydrochloride 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 Hydrochloride also inhibits dihydroorotate dehydrogenase (DHODH).
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SIRT-IN-1
0 ImagesSIRT-IN-1 is a potent inhibitor of SIRT1/2/3, with IC50s of 15, 10, 33 nM, respectively.
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SIRT6-IN-3
0 ImagesSIRT6-IN-3 (compound 8a) is a selective inhibitor of SIRT6 (IC50=7.49 μM). SIRT6-IN-3 inhibits pancreatic ductal adenocarcinoma (PDAC) cells proliferation and induces apoptosis. SIRT6-IN-3 increases the sensitivity of cancer cells to gemcitabine (HY-17026) via blocking the DNA damage repair pathway. SIRT6-IN-3 is used in pancreatic cancer research.
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RK-9123016
0 ImagesRK-9123016 is a potent inhibitor of SIRT2. RK-9123016 inhibits the enzymatic activity of SIRT2 with an IC50 value of 0.18 µM but not other human sirtuin members including SIRT1 and SIRT3 at 100 µM. RK-9123016 increases the acetylation level of eukaryotic translation initiation factor 5A (eIF5A), a physiological substrate of SIRT2, and reduces cell viability of human breast cancer cells accompanied with a decrease in c-Myc expression.
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JGB1741
0 ImagesSynonyms: ILS-JGB-1741JGB1741 (ILS-JGB-1741) is a potent and specific SIRT1 activity inhibitor with an IC50 of ∼15 μM. JGB1741 is a weak SIRT2 and SIRT3 inhibitor with an all IC50>100 μM. JGB1741 increases the acetylated p53 levels leading to p53-mediated apoptosis with modulation of Bax/Bcl2 ratio, cytochrome c release and PARP cleavage. JGB1741 has the potential for breast cancer research.
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Suramin
0 ImagesSuramin is a reversible and competitive protein-tyrosine phosphatases (PTPases) inhibitor. Suramin is a potent inhibitor of sirtuins: SirT1 (IC50=297 nM), SirT2 (IC50=1.15 μM), and SirT5 (IC50=22 μM). Suramin is a competitive inhibitor of reverse transcriptase (DNA topoisomerase II: IC50=5 μM). Suramin is a potent SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) inhibitor.Suramin efficiently inhibits IP5K and is an antiparasitic, anti-neoplastic and anti-angiogenic agent.
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SIRT5 inhibitor 4
0 ImagesSIRT5 inhibitor 4 (compound 11) is a potent, selective SIRT5 inhibitor with IC50 values of 26.4 and >400μM for SIRT5 and other SIRT subtype, respectively.
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FLS-359
0 ImagesCat. No.: HY-163532CAS No.: 2309398-79-4
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MIND4-19
0 ImagesMIND4-19 is a potent SIRT2 inhibitor with an IC50 value of 7.0 μM. MIND4-19 can be used for researching Huntington's disease.
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SirReal1-O-propargyl
0 ImagesCat. No.: HY-107453CAS No.: 1862237-99-7Synonyms: PROTAC Sirt2-binding moiety 1SirReal1-O-propargyl is a selective and highly potent Sirtuin 2 (Sirt2) inhibitor, with an IC50 of 2.4 μM. SirReal1-O-propargyl, the SirReal1-based moiety, binds to the cereblon ligand via a linker to form PROTAC to degrade Sirt2. SirReal1-O-propargyl is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
