SIRT3
SIRT3 is the major mitochondrial protein lysine deacetylase and regulates mitochondrial homeostasis by deacetylating proteins involved in energy metabolism, antioxidant defense, and redox adaptation[1][2]. Mechanistically, SIRT3 limits mitochondrial oxidative damage through targets including SOD2, PRDX3, COX4I2, and ALDH2, thereby linking lysine acetylation to reactive oxygen species control, respiratory-chain function, and aldehyde detoxification[3][4][5][6]. In disease models, SIRT3 deletion promotes endothelial dysfunction, vascular inflammation, vascular hypertrophy, and age-dependent hypertension, whereas SIRT3 overexpression reduces vascular oxidative stress and attenuates angiotensin II- and deoxycorticosterone acetate-salt-induced hypertension[3]. In intestinal ischemia/reperfusion injury, SIRT3-mediated PRDX3 deacetylation reduces mitochondrial oxidative damage and apoptosis; in osteoarthritis models, SIRT3 deacetylates COX4I2 to maintain mitochondrial respiratory-chain homeostasis and protect cartilage integrity[4][5]. Compared with related isoforms, SIRT3 differs experimentally because it localizes to mitochondria, whereas structurally similar SIRT1 and SIRT2 localize primarily to the nucleus and cytosol[1]. For experimental applications, honokiol activates SIRT3 in osteoarthritis models, while mitochondria-targeted SIRT3 inhibitors increase MnSOD acetylation with limited effects on known SIRT1 and SIRT2 targets[5][1].
References:
- [1]. Troelsen KS, Bæk M, Nielsen AL, Madsen AS, Rajabi N, Olsen CA. Mitochondria-targeted inhibitors of the human SIRT3 lysine deacetylase. RSC Chem Biol. 2021 Feb 1;2(2):627-635. [Content Brief]
- [2]. Sack MN. The role of SIRT3 in mitochondrial homeostasis and cardiac adaptation to hypertrophy and aging. J Mol Cell Cardiol. 2012 Mar;52(3):520-5. doi: 10.1016/j.yjmcc.2011.11.004. Epub 2011 Nov 19. PMID: 22119802; PMCID: PMC3294048. et al. The role of SIRT3 in mitochondrial homeostasis and cardiac adaptation to hypertrophy and aging. J Mol Cell Cardiol. 2012 Mar;52(3):520-5. [Content Brief]
- [3]. Dikalova AE, et al. Mitochondrial Deacetylase Sirt3 Reduces Vascular Dysfunction and Hypertension While Sirt3 Depletion in Essential Hypertension Is Linked to Vascular Inflammation and Oxidative Stress. Circ Res. 2020 Feb 14;126(4):439-452. [Content Brief]
- [4]. Wang Z, et al. SIRT3-mediated deacetylation of PRDX3 alleviates mitochondrial oxidative damage and apoptosis induced by intestinal ischemia/reperfusion injury. Redox Biol. 2020 Jan;28:101343. [Content Brief]
- [5]. Zhang Y, et al. Reprogramming of Mitochondrial Respiratory Chain Complex by Targeting SIRT3-COX4I2 Axis Attenuates Osteoarthritis Progression. Adv Sci (Weinh). 2023 Apr;10(10):e2206144. [Content Brief]
- [6]. Harris PS, et al. Characterizing Sirtuin 3 Deacetylase Affinity for Aldehyde Dehydrogenase 2. Chem Res Toxicol. 2017 Mar 20;30(3):785-793. [Content Brief]
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SIRT3 Related Products (42)
Related Products (42)
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Antibodies (1)
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SKLB-11A
0 ImagesSKLB-11A is a selective, orally active and allosteric SIRT3 (sirtuin 3) agonist with a Kd value of 4.7 μM. SKLB-11A is highly selective for other members of the SIRT family. SKLB-11A activates autophagy-related signaling pathways, prevents mitochondrial dysfunction, improves cardiac function in Doxorubicin (HY-15142A)-induced cardiotoxicity and myocardial ischemia/reperfusion models.
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Nicotinamide riboside malate
0 ImagesNicotinamide riboside malate, an orally active NAD+ precursor, increases NAD+ levels and activates SIRT1 and SIRT3. Nicotinamide riboside malate is a source of vitamin B3 (niacin) and enhances oxidative metabolism, protection against high fat diet-induced metabolic abnormalities. Nicotinamide riboside malate reduces cognitive deterioration in a transgenic mouse model of Alzheimer’s disease.
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4'-Bromo-resveratrol
0 ImagesSynonyms: 4′‐BR4'-Bromo-resveratrol (4′‐BR) is a dual SIRT1/SIRT3 inhibitor with an IC50 of 0.2 mM for both targets. 4'-Bromo-resveratrol induces caspase-dependent apoptosis, induces G0/G1 cell cycle arrest, and inhiibits proliferation. 4'-Bromo-resveratrol reduces lactate production, glucose uptake, and NAD+/NADH ratio, and downregulates lactate dehydrogenase A and glucose transporter 1 (GLUT1). 4'-Bromo-resveratrol can be used for the research of melanoma.
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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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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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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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Nicotinamide riboside tartrate
0 ImagesNicotinamide riboside tartrate, an orally active NAD+ precursor, increases NAD+ levels and activates SIRT1 and SIRT3. Nicotinamide riboside tartrate is a source of vitamin B3 (niacin) and enhances oxidative metabolism, protection against high fat diet-induced metabolic abnormalities. Nicotinamide riboside tartrate reduces cognitive deterioration in a transgenic mouse model of Alzheimer’s disease.
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MitoPBN
0 ImagesCat. No.: HY-136855CAS No.: 652968-37-1MitoPBN is a AMPK/SIRT3/PGC-1α axis modulator, reactive oxygen species scavenger and mitochondrial function enhancer. MitoPBN increases the phosphorylation level of AMPK, restores SIRT3 expression and reverses the down-regulation of PGC-1α, thereby promoting mitochondrial biogenesis. MitoPBN regulates glucose metabolism, reduces blood glucose by inhibiting hepatic gluconeogenesis and increasing hepatic glucose uptake, while scavenging mitochondrial superoxide anion/hydrogen peroxide, maintaining membrane potential and increasing ATP production. MitoPBN also reduces cell apoptosis, improves sperm motility, survival rate and membrane integrity, but may induce reductive stress in cryopreserved sperm at high concentrations. MitoPBN is widely applicable to research related to diabetes and type 2 diabetes.
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Nicotinamide riboside
0 ImagesNicotinamide riboside, an orally active NAD+ precursor, increases NAD+ levels and activates SIRT1 and SIRT3. Nicotinamide riboside is a source of vitamin B3 (niacin) and enhances oxidative metabolism, protection against high fat diet-induced metabolic abnormalities. Nicotinamide riboside reduces cognitive deterioration in a transgenic mouse model of Alzheimer’s disease.
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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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SPC-180002
0 ImagesCat. No.: HY-155784CAS No.: 2170274-53-8SPC-180002 is a SIRT1/3 dual inhibitor, with IC50 values of 1.13 and 5.41 μM, respectively. SPC-180002 disturbs redox homeostasis via ROS generation, which leads to an increase in both p21 protein stability and mitochondrial dysfunction. SPC-180002 strongly inhibits cell cycle progression and cancer cell growth. SPC-180002 activates the Nrf2 signaling pathway.
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hsa62
0 ImagesCat. No.: HY-160944CAS No.: 780822-35-7
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C1A
0 ImagesCat. No.: HY-124946CAS No.: 1021463-02-4
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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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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.
