組蛋白去乙�；敢种苿￢orinostat在神經生物學中的應用
Vorinostat (SAHA, MK0683，AbMole，M1780) 是一種廣譜的泛組蛋白去乙酰化酶抑制劑（HDACi）。其化學結構屬于丁二酰亞胺羥肟酸類化合物，能夠通過直接與HDACs結合并抑制其活性，增加乙酰化組蛋白的積累，從而調節(jié)細胞中的基因表達，并影響多個信號通路。此外，Vorinostat（MK0683）還具有細胞周期阻滯、凋亡、抑制血管生成等生物活性。研究表明，Vorinostat還可雙向調控應激反應基因的表達（如sod-3、hsp-16.2、skn-1等），Vorinostat在低濃度時上調上述基因的表達，而在高濃度（10μM）時則呈現抑制或中性效應，顯示出劑量依賴性的表觀遺傳調控特性[1]。Vorinostat還可通過降低Akt信號通路的表達水平，誘導細胞周期阻滯和程序性死亡[2]。此外，Vorinostat還可下調多種表觀遺傳調控酶（如EZH2、SUV39H1/2、DOT1L等）的表達，說明其對表觀遺傳調控網絡具有廣泛的影響[3]。在科研應用中，Vorinostat (SAHA)展現出多方面的潛力。首先Vorinostat可抑制多種腫瘤細胞的增殖，例如結腸癌細胞（HCT116、HT29）[4]、胰腺癌細胞（AsPC-1）[5]、肝癌細胞（LCL-PI 11）[5]、頭頸部鱗癌（HNSCC）等[6]。Vorinostat還可用于抑制寄生蟲，其機制同樣涉及原蟲細胞中HDAC的抑制[7]。值得注意的是，組織轉谷氨酰胺酶（TG2）的活性狀態(tài)會影響細胞對Vorinostat的敏感性。研究發(fā)現TG2活性的抑制可增強Vorinostat的抗增殖效應，而TG2過表達則導致細胞耐受性的獲得，提示TG2是Vorinostat耐受機制中的關鍵靶點[8]。在神經保護領域，Vorinostat可逆轉β淀粉樣蛋白（Amyloid β Protein）誘導的神經損傷，該生物學活性涉及對AKT-MDM2-p53通路的調控[9]。AbMole為全球科研客戶提供高純度、高生物活性的抑制劑、細胞因子、人源單抗、天然產物、熒光染料、多肽、靶點蛋白、化合物庫、抗生素等科研試劑，全球大量文獻專利引用。
范例詳解
BMC Cancer. 2016 Nov 7;16(1):857.
科研人員在該文章中探究了Vorinostat對小細胞肺癌（SCLC）的抑制作用及聯(lián)合抑制方案的開發(fā)。研究通過體外（H209、H146 細胞系）和體內（H209 異種移植裸鼠）實驗，證實 Vorinostat（HDAC 抑制劑）與順鉑（Cisplatin）聯(lián)合或與Etoposide (VP-16-213) 聯(lián)合使用時，能比單一處理組更顯著地抑制腫瘤細胞的活力、并誘導凋亡（激活 caspase-3、促進 PARP 裂解），以及誘導腫瘤細胞周期的S期阻滯，同時提高組蛋白H3和α-微管蛋白的乙酰化水平并持續(xù)抑制胸苷酸合成酶（TS）表達。本文的核心研究對象 Vorinostat (SAHA, MK0683，AbMole，M1780) 由AbMole提供。2014年，AbMole的兩款抑制劑分別被西班牙國家心血管研究中心和美國哥倫比亞大學用于動物體內實驗，相關科研成果發(fā)表于頂刊 Nature 和 Nature Medicine。
AbMole是ChemBridge中國區(qū)官方指定合作伙伴。
參考文獻及鳴謝
[1] S. Huang, H. Shi, Z. Shi, et al., Vorinostat, a potential hormetin, extends lifespan and enhances stress resistance via the SKN-1 pathway in Caenorhabditis elegans, Biogerontology 26(3) (2025) 97.
[2] S. Takeuchi, T. Hase, S. Shimizu, et al., Phase I study of vorinostat with gefitinib in BIM deletion polymorphism/epidermal growth factor receptor mutation double-positive lung cancer, Cancer science 111(2) (2020) 561-570.
[3] V. Maksimova, J. Makus, V. Popova, et al., Histone Methyltransferases as a New Target for Epigenetic Action of Vorinostat, Biochemistry. Biokhimiia 88(7) (2023) 968-978.
[4] M. Yousefian, M. Hashemi, V. Eskandarpour, et al., New indolin-2-ones, possessing sunitinib scaffold as HDAC inhibitors and anti-cancer agents with potential VEGFR inhibition activity; design, synthesis and biological evaluation, Bioorganic chemistry 156 (2025) 108231.
[5] M. Sanaei, F. Kavoosi, Effect of vorinostat on INK4 family and HDACs 1, 2, and 3 in pancreatic cancer and hepatocellular carcinoma, Research in pharmaceutical sciences 16(3) (2021) 260-268.
[6] N. Tanaka, A. A. Patel, L. Tang, et al., Replication Stress Leading to Apoptosis within the S-phase Contributes to Synergism between Vorinostat and AZD1775 in HNSCC Harboring High-Risk TP53 Mutation, Clinical cancer research : an official journal of the American Association for Cancer Research 23(21) (2017) 6541-6554.
[7] H. Li, E. M. Galon, S. Ji, et al., In vitro screening of compounds from the Food and Drug Administration-approved library identifies anti-Babesia gibsoni activity of idarubicin hydrochloride and vorinostat, Parasitology international 96 (2023) 102774.
[8] C. Carbone, E. Di Gennaro, G. Piro, et al., Tissue transglutaminase (TG2) is involved in the resistance of cancer cells to the histone deacetylase (HDAC) inhibitor vorinostat, Amino acids 49(3) (2017) 517-528.
[9] J. Meng, Y. Li, M. Zhang, et al., A combination of curcumin, vorinostat and silibinin reverses Aβ-induced nerve cell toxicity via activation of AKT-MDM2-p53 pathway, PeerJ 7 (2019) e6716.
[10] R. Parveen, D. Harihar, B. P. Chatterji, Recent histone deacetylase inhibitors in cancer therapy, Cancer 129(21) (2023) 3372-3380.
[11] C. H. Pan, Y. F. Chang, M. S. Lee, et al., Vorinostat enhances the cisplatin-mediated anticancer effects in small cell lung cancer cells, BMC cancer 16(1) (2016) 857.
Transcriptional activity of histone deacetylase (HDAC) inhibitors[10].
范例詳解
BMC Cancer. 2016 Nov 7;16(1):857.
科研人員在該文章中探究了Vorinostat對小細胞肺癌（SCLC）的抑制作用及聯(lián)合抑制方案的開發(fā)。研究通過體外（H209、H146 細胞系）和體內（H209 異種移植裸鼠）實驗，證實 Vorinostat（HDAC 抑制劑）與順鉑（Cisplatin）聯(lián)合或與Etoposide (VP-16-213) 聯(lián)合使用時，能比單一處理組更顯著地抑制腫瘤細胞的活力、并誘導凋亡（激活 caspase-3、促進 PARP 裂解），以及誘導腫瘤細胞周期的S期阻滯，同時提高組蛋白H3和α-微管蛋白的乙酰化水平并持續(xù)抑制胸苷酸合成酶（TS）表達。本文的核心研究對象 Vorinostat (SAHA, MK0683，AbMole，M1780) 由AbMole提供。2014年，AbMole的兩款抑制劑分別被西班牙國家心血管研究中心和美國哥倫比亞大學用于動物體內實驗，相關科研成果發(fā)表于頂刊 Nature 和 Nature Medicine。
Cell cycle progression analysis of vorinostat in combination with cisplatin in SCLC cells[11].
AbMole是ChemBridge中國區(qū)官方指定合作伙伴。
參考文獻及鳴謝
[1] S. Huang, H. Shi, Z. Shi, et al., Vorinostat, a potential hormetin, extends lifespan and enhances stress resistance via the SKN-1 pathway in Caenorhabditis elegans, Biogerontology 26(3) (2025) 97.
[2] S. Takeuchi, T. Hase, S. Shimizu, et al., Phase I study of vorinostat with gefitinib in BIM deletion polymorphism/epidermal growth factor receptor mutation double-positive lung cancer, Cancer science 111(2) (2020) 561-570.
[3] V. Maksimova, J. Makus, V. Popova, et al., Histone Methyltransferases as a New Target for Epigenetic Action of Vorinostat, Biochemistry. Biokhimiia 88(7) (2023) 968-978.
[4] M. Yousefian, M. Hashemi, V. Eskandarpour, et al., New indolin-2-ones, possessing sunitinib scaffold as HDAC inhibitors and anti-cancer agents with potential VEGFR inhibition activity; design, synthesis and biological evaluation, Bioorganic chemistry 156 (2025) 108231.
[5] M. Sanaei, F. Kavoosi, Effect of vorinostat on INK4 family and HDACs 1, 2, and 3 in pancreatic cancer and hepatocellular carcinoma, Research in pharmaceutical sciences 16(3) (2021) 260-268.
[6] N. Tanaka, A. A. Patel, L. Tang, et al., Replication Stress Leading to Apoptosis within the S-phase Contributes to Synergism between Vorinostat and AZD1775 in HNSCC Harboring High-Risk TP53 Mutation, Clinical cancer research : an official journal of the American Association for Cancer Research 23(21) (2017) 6541-6554.
[7] H. Li, E. M. Galon, S. Ji, et al., In vitro screening of compounds from the Food and Drug Administration-approved library identifies anti-Babesia gibsoni activity of idarubicin hydrochloride and vorinostat, Parasitology international 96 (2023) 102774.
[8] C. Carbone, E. Di Gennaro, G. Piro, et al., Tissue transglutaminase (TG2) is involved in the resistance of cancer cells to the histone deacetylase (HDAC) inhibitor vorinostat, Amino acids 49(3) (2017) 517-528.
[9] J. Meng, Y. Li, M. Zhang, et al., A combination of curcumin, vorinostat and silibinin reverses Aβ-induced nerve cell toxicity via activation of AKT-MDM2-p53 pathway, PeerJ 7 (2019) e6716.
[10] R. Parveen, D. Harihar, B. P. Chatterji, Recent histone deacetylase inhibitors in cancer therapy, Cancer 129(21) (2023) 3372-3380.
[11] C. H. Pan, Y. F. Chang, M. S. Lee, et al., Vorinostat enhances the cisplatin-mediated anticancer effects in small cell lung cancer cells, BMC cancer 16(1) (2016) 857.
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