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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CHIC35
0 ImagesCat. No.: HY-111303CAS No.: 848193-72-6
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SIRT1/2/3-IN-2
0 ImagesCat. No.: HY-114906CAS No.: 388086-13-3SIRT1/2/3-IN-2 (compound 9) is a potent SIRT inhibitor, with inhibition rates of 27%, 72%, and 71% targeting SIRT1, SIRT2, and SIRT3, respectively, at 200 μM. SIRT3 is a potential tumor suppressor or promoter, and its increased transcription may be associated with lymph node-positive breast cancer and oral squamous cell carcinoma.
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Sirt2-IN-5
0 ImagesCat. No.: HY-115979CAS No.: 902456-47-7Sirt2-IN-5 is a potent SIRT2 inhibtor.
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NH4-6
0 ImagesCat. No.: HY-182412CAS No.: 2375182-58-2NH4-6 is a SIRT2 inhibitor with an IC50 of 0.032 μM against SIRT2 and an IC50 of 3 μM against SIRT1. NH4-6 inhibits the deacetylase activity of SIRT1. As a cytotoxic agent, NH4-6 reduces cancer cell viability, suppresses anchorage-independent growth of cancer cells, induces acetylation of α-tubulin, and promotes acetylation of p53. NH4-6 can be used in the research of breast cancer.
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2'/3'-O-Acetyl-ADP-ribose sodium
0 ImagesCat. No.: HY-150119CAS No.: 1312013-29-82'/3'-O-Acetyl-ADP-ribose sodium is an inhibitor of cell division and oocyte maturation. 2'/3'-O-Acetyl-ADP-ribose sodium causes delay or arrest of oocyte maturation and blastomere division in embryos. 2'/3'-O-Acetyl-ADP-ribose sodium is produced by Sir2 family deacetylases during the coupling of histone/protein deacetylation with β-NAD+ cleavage. In neutral or weakly alkaline aqueous solutions, the direct enzymatic product forms of 2'/3'-O-Acetyl-ADP-ribose sodium, namely the 2'-O-acetyl form and the 3'-O-acetyl form, undergo intramolecular lactone exchange reaction and interconvert with each other.
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Sirt1/2-IN-5
0 ImagesCat. No.: HY-136713CAS No.: 143034-06-4
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NCO-141
0 ImagesCat. No.: HY-185682CAS No.: 1382354-26-8NCO-141 is a selective SIRT2 inhibitor with an IC50 of 0.5 μM. NCO-141 induces cell apoptosis via caspase activation and mitochondrial superoxide anion production. NCO-141 induces cell autophagy by increasing LC3-II levels and autophagosome accumulation. NCO-141 is applicable to relevant research on leukemia.
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Sirt2-IN-6
0 ImagesCat. No.: HY-145958CAS No.: 2243151-81-5
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Nicotinamide hydrochloride
0 ImagesCat. No.: HY-B0150ACAS No.: 25334-23-0Synonyms: Niacinamide hydrochloride; Nicotinic acid amide hydrochlorideNicotinamide hydrochloride is a form of vitamin B3 or niacin. Nicotinamide hydrochloride inhibits SIRT2 activity (IC50: 2 μM). Nicotinamide hydrochloride also inhibits SIRT1. Nicotinamide hydrochloride increases cellular NAD+, ATP, ROS levels. Nicotinamide hydrochloride inhibits tumor growth and improves survival. Nicotinamide hydrochloride also has anti-HBV activity.
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hsa62
0 ImagesCat. No.: HY-160944CAS No.: 780822-35-7
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PROTAC Sirt2 Degrader-2
0 ImagesCat. No.: HY-179388CAS No.: 3123329-68-7PROTAC Sirt2 Degrader-2 is a highly efficient and selective PROTAC degrader targeting SIRT2. PROTAC Sirt2 Degrader-2 demonstrates the most potent anti-proliferative activity both in vitro and in vivo. PROTAC Sirt2 Degrader-2 leads to a marked increase in H4K16Ac levels. PROTAC Sirt2 Degrader-2 significantly suppresses clonogenic formation and migration, induces cell cycle arrest, and promotes apoptosis. PROTAC Sirt2 Degrader-2 inhibits the AKT/mTOR signaling pathway by indirectly degrading SIRT2 and blocking downstream protein phosphorylation, thereby disrupting the signaling cascade and suppressing tumor development. PROTAC Sirt2 Degrader-2 can be used for the study of ovarian cancer.
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Sirt1/2-IN-1
0 ImagesCat. No.: HY-146013CAS No.: 2402779-21-7
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SIRT2-IN-14
0 ImagesCat. No.: HY-160617CAS No.: 1884571-59-8SIRT2-IN-14 (Compound 78) is a selectve inhibitor for SIRT2 with an IC50 of 0.196 μM.
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NCO-90
0 ImagesCat. No.: HY-183870CAS No.: 1382354-18-8NCO-90 is a selective SIRT2 inhibitor with an IC50 of 1.0 μM. NCO-90 induces Apoptosis via Caspase activation and mitochondrial superoxide anion production, and also induces Autophagic cell death by increasing LC3-II levels and autophagosome accumulation. NCO-90 exhibits anticancer activity against leukemia. NCO-90 can be used in research related to acute lymphoblastic leukemia and acute myeloid leukemia.
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SL010110
0 ImagesCat. No.: HY-W197205CAS No.: 380173-90-0SL010110 is an anti-hyperglycemic agent. SL010110 potently inhibits gluconeogenesis by inhibiting SIRT2, activating p300, and subsequently promoting PEPCK1 degradation. SL010110 downregulates the protein level of PEPCK1 without affecting the gene expressions of PEPCK, glucose-6-phosphatase, and fructose-1,6-bisphosphatase. SL010110 significantly improves glucose homeostasis in type 2 diabetic (T2D) mice model. SL010110 can be used for T2D research.
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SR94
0 ImagesCat. No.: HY-W841840CAS No.: 550301-63-8
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SIRT6-IN-4
0 ImagesCat. No.: HY-170402CAS No.: 3075160-74-3SIRT6-IN-4 (Compound 10d) is a selective inhibitor for SIRT6 with an IC50 of 5.68 μM. SIRT6-IN-4 inhibits the proliferation of MCF-7 with an IC50 of 8.30 μM. SIRT6-IN-4 arrests the cell cycle at G2/M phase, inhibits thecell migration and invasion of MCF-7, and induces apoptosis. SIRT6-IN-4 exhibits antitumor efficacy in mouse models.
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PRMT/HKMT-IN-1
0 ImagesCat. No.: HY-114510CAS No.: 1020399-52-3PRMT/HKMT-IN-1 is an epigenetic multi-target protein arginine methyltransferases (PRMTs) and histone lysine methyltransferases (HKMTs) inhibitor. PRMT/HKMT-IN-1 inhibits Aspergillus nidulans RmtA with an IC50 of 29 μM. PRMT/HKMT-IN-1 inhibits human PRMT1, p300/CBP HAT, CARM1, SET7, SIRT1 and SIRT2. PRMT/HKMT-IN-1 inhibits methylation of histone H3K4, H4R3, and H3R17 residues. CBP/p300-IN-23 induces apoptosis, arrests cell cycle in S phase, and triggers granulocytic differentiation in leukemia cells. PRMT/HKMT-IN-1 can be used for the research of leukemia.
