Selisistat(EX527)抑制劑作為探索SIRT1功能的核心工具在科研中的應用
Selisistat（EX527，AbMole，M1708）是一種高效和高度選擇性的SIRT1（Sirtuin 1）抑制劑。Selisistat（EX527，AbMole，M1708）可結合SIRT1與煙酰胺腺嘌呤二核苷酸（NAD+）形成的復合物，從而阻斷SIRT1的去乙酰化活性。在科研應用中，Selisistat是探索SIRT1功能的核心工具之一。例如Selisistat（EX527）在代謝研究中，被用于揭示SIRT1對PPARα蛋白穩定性的調控機制，發現Selisistat可通過抑制SIRT1阻止PPARα的泛素化降解[1]。Selisistat在腫瘤模型中，可通過單獨或聯合其他化合物如紫杉醇（Paclitaxel）抑制腫瘤生長，其機制涉及調控細胞周期和細胞代謝的重編程[2]。在神經科學領域，Selisistat（EX527）可通過抑制SIRT1影響小膠質細胞的表型轉換，從而改變炎癥因子和活性氧的生成[3]。Selisistat在病毒的相關研究中，通過下調SIRT1活性顯著抑制了乙型肝炎病毒的復制[4]。Selisistat還具有其它生物學活性，其通過抑制SIRT1可影響多種細胞過程。例如在炎癥反應中，Selisistat（EX527）能夠逆轉白藜蘆醇對SIRT1的激活作用，進而減弱白藜蘆醇的抗炎效果[5]。在氧化應激模型中，Selisistat的處理會降低細胞線粒體功能并促進凋亡[6]。Selisistat還被用于解析SIRT1在細胞自噬中的作用[7]。在皮膚毛囊的再生研究中，Selisistat通過抑制鐵死亡通路促進了毛發再生[8]。
范例詳解
Int J Biol Sci. 2022 Jan 31;18(4):1594-1611
中科院上海藥物研究所、上海中醫藥大學的實驗人員在上述文章中研究了Atractylenolide III （白術內酯III，ATL III，一種從蒼術中提取的生物活性成分）對非酒精性脂肪性肝�。∟AFLD）的抑制潛力及其可能的機制。研究發現，ATL III通過激活肝臟中的脂肪素受體1（AdipoR1）介導的AMPK信號通路和SIRT1通路，改善了高脂飲食（HFD）誘導的NAFLD小鼠模型和游離脂肪酸（FFAs）處理的HepG2細胞中的肝損傷和脂質積累。在上述研究過程中，實驗人員使用了來自AbMole的Dorsomorphin（Compound C，AbMole，M2238）和Selisistat（EX527，AbMole，M1708）分別作為AMPK和SIRT1通路抑制劑，并證實了上述兩條通路是Atractylenolide III發揮生物活性的重要基礎。在細胞實驗中，科研人員還使用了AbMole的CCK-8試劑盒（AbMole，M4839）驗證了Atractylenolide III對FFAs處理的HepG2細胞活力的影響[9]。
AbMole是ChemBridge中國區官方指定合作伙伴。
參考文獻及鳴謝
[1] J. H. Suh, K. H. Kim, M. E. Conner, et al., Hepatic PPARalpha Is Destabilized by SIRT1 Deacetylase in Undernourished Male Mice, Frontiers in nutrition 9 (2022) 831879.
[2] A. Wawruszak, J. Luszczki, D. Bartuzi, et al., Selisistat, a SIRT1 inhibitor, enhances paclitaxel activity in luminal and triple-negative breast cancer: in silico, in vitro, and in vivo studies, Journal of enzyme inhibition and medicinal chemistry 40(1) (2025) 2458554.
[3] J. Zhu, P. Jin, T. Zhou, et al., SIRT1 modulates microglia phenotypes via inhibiting drp1 phosphorylation reduces neuroinflammation in heatstroke, Brain research bulletin 218 (2024) 111101.
[4] W. Zhang, J. Cui, L. Li, et al., Notoginsenoside R1 inhibits hepatitis B virus replication by modulating SIRT1 activity, Acta virologica 67(1) (2023) 51-58.
[5] X. M. Chen, Y. J. Guo, H. W. Ling, et al., The Effect of Resveratrol in Sirt1/CST Pathway to Inhibit TNF-alpha Induced Inflammatory Response in Rat Primary Fibroblast-Like Synoviocytes, Biological & pharmaceutical bulletin 46(11) (2023) 1592-1600.
[6] Y. Wang, Q. Yang, S. Shen, et al., Mst1 promotes mitochondrial dysfunction and apoptosis in oxidative stress-induced rheumatoid arthritis synoviocytes, Aging 12(16) (2020) 16211-16223.
[7] P. Cao, Y. Wang, C. Zhang, et al., Quercetin ameliorates nonalcoholic fatty liver disease (NAFLD) via the promotion of AMPK-mediated hepatic mitophagy, The Journal of nutritional biochemistry 120 (2023) 109414.
[8] Z. Zeng, B. Wang, M. Ibrar, et al., Schizochytrium sp. Extracted Lipids Prevent Alopecia by Enhancing Antioxidation and Inhibiting Ferroptosis of Dermal Papilla Cells, Antioxidants (Basel, Switzerland) 12(7) (2023).
[9] Q. Li, J. X. Tan, Y. He, et al., Atractylenolide III ameliorates Non-Alcoholic Fatty Liver Disease by activating Hepatic Adiponectin Receptor 1-Mediated AMPK Pathway, International journal of biological sciences 18(4) (2022) 1594-16
范例詳解
Int J Biol Sci. 2022 Jan 31;18(4):1594-1611
中科院上海藥物研究所、上海中醫藥大學的實驗人員在上述文章中研究了Atractylenolide III （白術內酯III，ATL III，一種從蒼術中提取的生物活性成分）對非酒精性脂肪性肝�。∟AFLD）的抑制潛力及其可能的機制。研究發現，ATL III通過激活肝臟中的脂肪素受體1（AdipoR1）介導的AMPK信號通路和SIRT1通路，改善了高脂飲食（HFD）誘導的NAFLD小鼠模型和游離脂肪酸（FFAs）處理的HepG2細胞中的肝損傷和脂質積累。在上述研究過程中，實驗人員使用了來自AbMole的Dorsomorphin（Compound C，AbMole，M2238）和Selisistat（EX527，AbMole，M1708）分別作為AMPK和SIRT1通路抑制劑，并證實了上述兩條通路是Atractylenolide III發揮生物活性的重要基礎。在細胞實驗中，科研人員還使用了AbMole的CCK-8試劑盒（AbMole，M4839）驗證了Atractylenolide III對FFAs處理的HepG2細胞活力的影響[9]。
ATL III administration reduces FFAs-induced lipid accumulation in HepG2 cell
AbMole是ChemBridge中國區官方指定合作伙伴。
參考文獻及鳴謝
[1] J. H. Suh, K. H. Kim, M. E. Conner, et al., Hepatic PPARalpha Is Destabilized by SIRT1 Deacetylase in Undernourished Male Mice, Frontiers in nutrition 9 (2022) 831879.
[2] A. Wawruszak, J. Luszczki, D. Bartuzi, et al., Selisistat, a SIRT1 inhibitor, enhances paclitaxel activity in luminal and triple-negative breast cancer: in silico, in vitro, and in vivo studies, Journal of enzyme inhibition and medicinal chemistry 40(1) (2025) 2458554.
[3] J. Zhu, P. Jin, T. Zhou, et al., SIRT1 modulates microglia phenotypes via inhibiting drp1 phosphorylation reduces neuroinflammation in heatstroke, Brain research bulletin 218 (2024) 111101.
[4] W. Zhang, J. Cui, L. Li, et al., Notoginsenoside R1 inhibits hepatitis B virus replication by modulating SIRT1 activity, Acta virologica 67(1) (2023) 51-58.
[5] X. M. Chen, Y. J. Guo, H. W. Ling, et al., The Effect of Resveratrol in Sirt1/CST Pathway to Inhibit TNF-alpha Induced Inflammatory Response in Rat Primary Fibroblast-Like Synoviocytes, Biological & pharmaceutical bulletin 46(11) (2023) 1592-1600.
[6] Y. Wang, Q. Yang, S. Shen, et al., Mst1 promotes mitochondrial dysfunction and apoptosis in oxidative stress-induced rheumatoid arthritis synoviocytes, Aging 12(16) (2020) 16211-16223.
[7] P. Cao, Y. Wang, C. Zhang, et al., Quercetin ameliorates nonalcoholic fatty liver disease (NAFLD) via the promotion of AMPK-mediated hepatic mitophagy, The Journal of nutritional biochemistry 120 (2023) 109414.
[8] Z. Zeng, B. Wang, M. Ibrar, et al., Schizochytrium sp. Extracted Lipids Prevent Alopecia by Enhancing Antioxidation and Inhibiting Ferroptosis of Dermal Papilla Cells, Antioxidants (Basel, Switzerland) 12(7) (2023).
[9] Q. Li, J. X. Tan, Y. He, et al., Atractylenolide III ameliorates Non-Alcoholic Fatty Liver Disease by activating Hepatic Adiponectin Receptor 1-Mediated AMPK Pathway, International journal of biological sciences 18(4) (2022) 1594-16
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