OSS_128167 is a potent selective silencing regulatory protein 6 (SIRT6) inhibitor with an IC50 of 89 μM[1]. OSS_128167 can inhibit HBV transcription and replication, and has antiviral and anti-inflammatory effects[2-3].
OSS_128167(0-200 μM;24h) can promote the increase of H3K9 acetylation, the decrease of TNF-α secretion, the up-regulation of GLUT-1, and the increase of glucose uptake in BxPC-3 cells[1]. OSS_128167(10 μM-50 μM OSS_128167; 24 h) can reverse the protective effect of Oridonin (Ori) on Doxorubicin induced cardiotoxicity (DIC) [4]. OSS_128167 attenuated ROS generation and protective polarization caused by Caffeic acid phenethyl ester (CAPE) pretreatment[5].
OSS_128167(OSS-128167 in a final concentration of 12 mg/mL in a solution containing 2% DMSO, 40% PEG 300, and 2% Tween-80; 100 mg/kg; i.v) treatment caused increased toe swelling in collagen-induced arthritis (CIA) rats, and the proportion of CD38+ NK cells in peripheral blood of CIA rats increased[6]. OSS_128167(80 mg/kg;i.p;1h) significantly accelerated LPS-induced loss of tight junction proteins, lung inflammation, and apoptosis[7].
References:
[1]. Parenti MD, Grozio A, et,al. Discovery of novel and selective SIRT6 inhibitors. J Med Chem. 2014 Jun 12;57(11):4796-804. doi: 10.1021/jm500487d. Epub 2014 May 19. PMID: 24785705.
[2]. Jiang H, Cheng ST, et,al. SIRT6 Inhibitor, OSS_128167 Restricts Hepatitis B Virus Transcription and Replication Through Targeting Transcription Factor Peroxisome Proliferator-Activated Receptors α. Front Pharmacol. 2019 Oct 25;10:1270. doi: 10.3389/fphar.2019.01270. PMID: 31708789; PMCID: PMC6823301.
[3]. Cea M, Cagnetta A, et,al. Evidence for a role of the histone deacetylase SIRT6 in DNA damage response of multiple myeloma cells. Blood. 2016 Mar 3;127(9):1138-50. doi: 10.1182/blood-2015-06-649970. Epub 2015 Dec 16. PMID: 26675349; PMCID: PMC4778164.
[4]. Yu D, Li J, et,al. Oridonin ameliorates doxorubicin induced-cardiotoxicity via the E2F1/Sirt6/PGC1α pathway in mice. Food Chem Toxicol. 2023 Nov;181:114050. doi: 10.1016/j.fct.2023.114050. Epub 2023 Sep 20. PMID: 37734463.
[5]. Wang Y, Cai Z, et,al. Caffeic Acid Phenethyl Ester Suppresses Oxidative Stress and Regulates M1/M2 Microglia Polarization via Sirt6/Nrf2 Pathway to Mitigate Cognitive Impairment in Aged Mice following Anesthesia and Surgery. Antioxidants (Basel). 2023 Mar 13;12(3):714. doi: 10.3390/antiox12030714. PMID: 36978961; PMCID: PMC10045012.
[6]. Wang H, Li S, et,al. Potential therapeutic effects of cyanidin-3-O-glucoside on rheumatoid arthritis by relieving inhibition of CD38+ NK cells on Treg cell differentiation. Arthritis Res Ther. 2019 Oct 28;21(1):220. doi: 10.1186/s13075-019-2001-0. PMID: 31661005; PMCID: PMC6819496.
[7]. Liu H, Wang S, et,al. SIRT6 ameliorates LPS-induced apoptosis and tight junction injury in ARDS through the ERK1/2 pathway and autophagy. Int J Med Sci. 2023 Mar 5;20(5):581-594. doi: 10.7150/ijms.80920. PMID: 37082736; PMCID: PMC10110478.
OSS_128167是一种有效的选择性沉默调节蛋白6 (SIRT6)抑制剂，IC50为89 μM[1]。OSS_128167能抑制HBV转录和复制，并具有抗病毒和抗炎作用[2-3]。
OSS_128167(0 ~ 200 μM;24h)能促进BxPC-3细胞H3K9乙酰化水平升高、TNF-α分泌减少、GLUT-1表达上调、葡萄糖摄取增加[1]。OSS_128167(10 μm -50 μm;24 h)可逆转Oriidonin (Ori)对阿霉素致心脏毒性(DIC)的保护作用[4]。OSS_128167可减弱咖啡酸苯乙酯(CAPE)预处理引起的ROS生成和保护性极化[5]。
OSS_128167(OSS-128167 in a final concentration of 12 mg/mL in a solution containing 2% DMSO, 40% PEG 300, and 2% Tween-80; 100 mg/kg; i.v)处理导致胶原诱导性关节炎CIA大鼠足趾肿胀加重，外周血CD38+ NK细胞比例升高[6]。OSS_128167(80 mg/kg;i.p;1h)在小鼠中显著加速LPS诱导的紧密连接蛋白丢失、肺部炎症和细胞凋亡[7]。