Vorinostat (SAHA, MK0683, AbMole, M1780) is a broad-spectrum, pan-histone deacetylase inhibitor (HDACi). Belonging to the succinylhydroxamic acid class of compounds, it directly binds to and inhibits HDAC activity, leading to the accumulation of acetylated histones, thereby regulating gene expression and affecting multiple signaling pathways. Additionally, Vorinostat (MK0683) exhibits bioactivities including cell cycle arrest, apoptosis, and inhibition of angiogenesis. Studies have shown that Vorinostat bidirectionally regulates stress response genes (e.g., sod-3, hsp-16.2, skn-1). It upregulates these genes at low concentrations but exhibits inhibitory or neutral effects at high concentrations (10 μM), demonstrating dose-dependent epigenetic regulatory properties [1]. Vorinostat also induces cell cycle arrest and programmed cell death by downregulating the Akt signaling pathway [2]. Furthermore, Vorinostat downregulates multiple epigenetic regulatory enzymes (e.g., EZH2, SUV39H1/2, DOT1L), indicating its broad impact on the epigenetic regulatory network [3].
In research applications, Vorinostat (SAHA) has shown multifaceted potential. First, it inhibits the proliferation of various tumor cells, including colon cancer cells (HCT116, HT29) [4], pancreatic cancer cells (AsPC-1) [5], hepatocellular carcinoma cells (LCL-PI 11) [5], and head and neck squamous cell carcinoma (HNSCC) cells [6]. Vorinostat is also used to inhibit parasites, with the mechanism similarly involving HDAC inhibition in protozoan cells [7]. Notably, the activity status of tissue transglutaminase 2 (TG2) affects cellular sensitivity to Vorinostat. Inhibition of TG2 activity enhances the anti-proliferative effect of Vorinostat, whereas TG2 overexpression confers resistance, identifying TG2 as a key target in Vorinostat tolerance mechanisms [8]. In the field of neuroprotection, Vorinostat reverses amyloid β protein -induced neural damage, an activity involving regulation of the AKT-MDM2-p53 pathway [9].
AbMole provides global researchers with high-purity, high-bioactivity inhibitors, cytokines, human monoclonal antibodies, natural products, fluorescent dyes, peptides, compound libraries, antibiotics, and other research reagents, widely cited in numerous publications and patents worldwide.
Case Study
BMC Cancer. 2016 Nov 7;16(1):857. In this study, researchers investigated the inhibitory effect of Vorinostat on small cell lung cancer (SCLC) and the development of combination therapy strategies. Through in vitro (H209, H146 cell lines) and in vivo (H209 xenograft nude mouse model) experiments, the study demonstrated that Vorinostat (an HDAC inhibitor), when combined with Cisplatin or with Etoposide (VP-16-213), more significantly inhibited tumor cell viability, induced apoptosis (via caspase-3 activation and PARP cleavage), and induced S-phase cell cycle arrest compared to single-agent treatments. The combination also increased acetylation levels of histone H3 and α-tubulin while persistently inhibiting thymidylate synthase (TS) expression. The core research compound, Vorinostat (SAHA, MK0683, AbMole, M1780), was provided by AbMole. In 2014, two inhibitors from AbMole were used in in vivo studies by the Spanish National Center for Cardiovascular Research (CNIC) and Columbia University, leading to research publications in Nature and Nature Medicine.
References and Acknowledgements
[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.