A4084-500mg | Vorinostat (SAHA, MK0683) [149647-78-9] Clinisciences

Background

Vorinostat (suberoylanilide hydroxamic acid, SAHA) is a histone deacetylase inhibitor (HDACi), that plays key roles in epigenetic or non-epigenetic regulation, inducing growth arrest, differentiation and apoptosis of tumor cells.^[1] Vorinostat is a small molecular with the formular of C₁₄H₂₀N₂O₃ and molecular weight of 264.3. The major mechanism of HDACi-induced apoptosis is the activation of the intrinsic apoptotic pathway. HDACi can activate the intrinsic apoptotic pathway by releasing of cytochrome c from mitochondria and regulating of Bcl-2 family expression.^[2]

Reference

[1] Hui-ming Z, Qian-hai D, Wei-ping C, Ru-bin L. Vorinostat, a HDAC inhibitor, showed anti-osteoarthritic activities through inhibition of iNOS and MMP expression, p38 and ERK phosphorylation and blocking NF-kB nuclear translocation. International Immunopharmacology. 2013, 17. 329-335.

[2] Norihisa U, Sayaka K, Hisanori M, Katsuhiko Y, Airo T. Requirement of p38 MAPK for a cell-death pathway triggered by vorinostat in MDA-MB-231 human breast cancer cells. Cancer Letters. 2012, 315. 112-121.

Product Citation

1. Joseph Boyle, Derick Chiappo, et al. "Aminocoumarin-based heme oxygenase activity fluorescence probe reveals novel aspects of HO-1 regulation." Research Square. 22 Nov, 2023.
2. Aran Merati, Spandana Kotian, et al. "Glioma Stem Cells Are Sensitized to BCL-2 Family Inhibition by Compromising Histone Deacetylases." Int J Mol Sci. 2023 Sep 5;24(18):13688. PMID: 37761989
3. Spandana Kotian, Rachel M Carnes, et al. "Enhancing Transcriptional Reprogramming of Mesenchymal Glioblastoma with Grainyhead-like 2 and HDAC Inhibitors Leads to Apoptosis and Cell-Cycle Dysregulation." Genes (Basel). 2023 Sep 12;14(9):1787. PMID: 37761927
4. Shelby M. Knoche, Gabrielle L. Brumfield, et al. "The histone deacetylase inhibitor M344 as a multifaceted therapy for pancreatic cancer." PLoS One. 2022 Sep 20;17(9):e0273518. PMID: 36126055
5. Phoebe McCrorie, Jonathan Rowlinson, et al. "Detection of Label-Free Drugs within Brain Tissue Using Orbitrap Secondary Ion Mass Spectrometry as a Complement to Neuro-Oncological Drug Delivery." Pharmaceutics. 2022 Mar 5;14(3):571. PMID: 35335947
6. Nora-Guadalupe P Ramirez, Jeon Lee, et al. "ADAP1 promotes latent HIV-1 reactivation by selectively tuning KRAS–ERK–AP-1 T cell signaling-transcriptional axis." Nat Commun. 2022 Mar 1;13(1):1109. PMID: 35232997
7. Yanhong Xu, Shiqiao Peng, et al. "High doses of butyrate induce a reversible body temperature drop through transient proton leak in mitochondria of brain neurons." Life Sci. 2021 Aug 1;278:119614. PMID: 34022200
8. Maojun Zhou, Hao Zheng, et al. "Discovery of a novel AR/HDAC6 dual inhibitor for prostate cancer treatment." Aging (Albany NY). 2021 Feb 17;13(5):6982-6998. PMID: 33621955
9. Haiyang Yu, Shan Lu, et al. "TDP-43 and HSP70 phase separate into anisotropic, intranuclear liquid spherical annuli." bioRxiv. March 29, 2020.
10. Liu W, Song YY, et al. "Dysregulation of FOXO transcription factors in Epstein-Barr virus-associated gastric carcinoma." Virus Res. 2020;276:197808. PMID: 31712122
11. Emily L Morton, Christian V Forst, et al. "Transcriptional Circuit Fragility Influences HIV Proviral Fate." bioRxiv. 2018 December 23.
12. Feng XL, Deng HB, et al. "Suberoylanilide Hydroxamic Acid Triggers Autophagy by Influencing the mTOR Pathway in the Spinal Dorsal Horn in a Rat Neuropathic Pain Model." Neurochem Res. 2018 Dec 17. PMID: 30560396
13. Deng R, Zhang P, et al. "HDAC is indispensable for IFN-γ-induced B7-H1 expression in gastric cancer." Clin Epigenetics. 2018 Dec 11;10(1):153. PMID: 30537988
14. Kim SR, Lewis JM, et al. "BET inhibition in advanced cutaneous T cell lymphoma is synergistically potentiated by BCL2 inhibition or HDAC inhibition." Oncotarget. 2018 Jun 26;9(49):29193-29207. PMID: 30018745
15. Hari Prasad, Rajini Rao. "The Amyloid Clearance Defect in ApoE4 Astrocytes is Corrected by Epigenetic Restoration of NHE6." bioRxiv. 2018.January. 4 PMID: 29498802
16. Mirza AN, Fry MA, et al. "Combined inhibition of atypical PKC and histone deacetylase 1 is cooperative in basal cell carcinoma treatment." JCI Insight. 2017 Nov 2;2(21). pii: 97071. PMID: 29093271
17. Hai Y, Shinsky SA, et al. "Histone deacetylase 10 structure and molecular function as a polyamine deacetylase." Nat Commun. 2017 May 18;8:15368. PMID: 28516954
18. Bagnall NH, Hines BM, et al. "Insecticidal activities of histone deacetylase inhibitors against a dipteran parasite of sheep, Lucilia cuprina." Int J Parasitol Drugs Drug Resist. 2017 Apr;7(1):51-60. PMID: 28110187
19. Sun, Yuefeng, et al. "Fe65 Suppresses Breast Cancer Cell Migration and Invasion through Tip60 Mediated Cortactin Acetylation." Scientific reports 5 (2015). PMID: 26166158

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Chemical Properties

Physical Appearance	A solid
Storage	Store at -20°C
M.Wt	264.3
Cas No.	149647-78-9
Formula	C₁₄H₂₀N₂O₃
Synonyms	SAHA, suberoylanilide hydroxamic acid, Suberanilohydroxamic acid, SAHA cpd
Solubility	insoluble in EtOH; insoluble in H2O; ≥4.41 mg/mL in DMSO
Chemical Name	N'-hydroxy-N-phenyloctanediamide
SDF	Download SDF
Canonical SMILES	C1=CC=C(C=C1)NC(=O)CCCCCCC(=O)NO
Shipping Condition	Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice.
General tips	We do not recommend long-term storage for the solution, please use it up soon.

Protocol

Cell experiment: [1]
Cell lines	Human cutaneous T-cell lymphomas (CTCL) cell lines
Preparation method	The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37°C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.
Reaction Conditions	IC50: 0.146 μM (HH)、2.062 μM (HuT)、78 2.697 μM (MJ)、1.375 μM (MylA)、1.510 μM (SeAx); 72h
Applications	Vorinostat dose-dependently reduced cell proliferation with IC50 values of 0.146 μM, 2.062 μM, 2.697 μM, 1.375 μM and 1.510 μM in HH, HuT78, MJ, MylA and SeAx cells, respectively.
Animal experiment : [2]
Animal models	C57BL/6 mice bearing Eμ-myc lymphomas
Dosage form	C57BL/6 mice bearing Eμ-myc lymphomas were injected with vorinostat (200 mg/kg i.p.) and lymphoma cells were harvested after the indicated time points. The percentage of tumor cells in the lymph node of C57BL/6 mice bearing Eμ-myc lymphomas treated with vorinostat was determined by FACS analysis.
Applications	Vorinostat induced a marked accumulation of Eμ-myc lymphomas displaying DNA fragmentation in vivo.
Other notes	Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
References: [1] Wozniak M B, Villuendas R, Bischoff J R, et al. Vorinostat interferes with the signaling transduction pathway of T cell receptor and synergizes with PI3K inhibitors in cutaneous T-cell lymphoma. haematologica, 2010: haematol. 2009.013870. [2] Lindemann R K, Newbold A, Whitecross K F, et al. Analysis of the apoptotic and therapeutic activities of histone deacetylase inhibitors by using a mouse model of B cell lymphoma. Proceedings of the National Academy of Sciences, 2007, 104(19): 8071-8076.