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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
Chemical Compound Review

NHNPODA     N'-hydroxy-N-phenyl- octanediamide

Synonyms: Zolinza, Vorinostat, SAHA, vorinostatum, CHEMBL98, ...
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Disease relevance of SAHA cpd


Psychiatry related information on SAHA cpd


High impact information on SAHA cpd

  • HDAC inhibitors, such as trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA), have anti-tumour effects, as they can inhibit cell growth, induce terminal differentiation and prevent the formation of tumours in mice models, and they are effective in the treatment of promyelocytic leukemia [9].
  • Studies (x-ray crystallographic) showed that the catalytic site of HDAC has a tubular structure with a zinc atom at its base and that these HDAC inhibitors, such as suberoylanilide hydroxamic acid and trichostatin A, fit into this structure with the hydroxamic moiety of the inhibitor binding to the zinc [10].
  • We found striking differences among these cancer cells in constitutive expression and response to suberoylanilide hydroxamic acid in levels of antiapoptotic and proapoptotic proteins, mitochondria membrane integrity, activation of caspases, ROS accumulation, and expression of thioredoxin, the major scavenger of ROS [3].
  • Although p16(INK4A) did not affect the genome-wide transcription changes mediated by SAHA, a small number of apoptotic genes, including BCLXL and B-MYB, were differentially regulated in a manner consistent with attenuated HDACi-mediated apoptosis in arrested cells [11].
  • Transfection of transformed cells with Trx small interfering RNA caused a marked decrease in the level of Trx protein with an increase in ROS, a decrease in cell proliferation, and an increase in sensitivity to SAHA-induced cell death [12].

Chemical compound and disease context of SAHA cpd


Biological context of SAHA cpd

  • We found that MM cells are irreversibly committed to cell death within few hours of incubation with SAHA [4].
  • Within 1 h, SAHA caused modifications in acetylation and methylation of core histones and increased DNase I sensitivity and restriction enzyme accessibility in the p21(WAF1) promoter [18].
  • Thus, this study identifies effects of SAHA on p21(WAF1)-associated proteins that explain, at least in part, the selective effect of HDACi in altering gene expression [18].
  • Here we studied SAHA-induced changes in the p21(WAF1) promoter of ARP-1 cells to better understand the mechanism of HDACi gene activation [18].
  • We demonstrate that the HDACis suberoylanilide hydroxamic acid (SAHA) and depsipeptide regulate a highly overlapping gene set with at least 22% of genes showing altered expression over a 16-h culture period [11].

Anatomical context of SAHA cpd


Associations of SAHA cpd with other chemical compounds


Gene context of SAHA cpd


Analytical, diagnostic and therapeutic context of SAHA cpd


  1. Differential and epigenetic gene expression profiling identifies frequent disruption of the RELN pathway in pancreatic cancers. Sato, N., Fukushima, N., Chang, R., Matsubayashi, H., Goggins, M. Gastroenterology (2006) [Pubmed]
  2. Dimethyl sulfoxide to vorinostat: development of this histone deacetylase inhibitor as an anticancer drug. Marks, P.A., Breslow, R. Nat. Biotechnol. (2007) [Pubmed]
  3. Intrinsic apoptotic and thioredoxin pathways in human prostate cancer cell response to histone deacetylase inhibitor. Xu, W., Ngo, L., Perez, G., Dokmanovic, M., Marks, P.A. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  4. Transcriptional signature of histone deacetylase inhibition in multiple myeloma: biological and clinical implications. Mitsiades, C.S., Mitsiades, N.S., McMullan, C.J., Poulaki, V., Shringarpure, R., Hideshima, T., Akiyama, M., Chauhan, D., Munshi, N., Gu, X., Bailey, C., Joseph, M., Libermann, T.A., Richon, V.M., Marks, P.A., Anderson, K.C. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  5. Induction of polyploidy by histone deacetylase inhibitor: a pathway for antitumor effects. Xu, W.S., Perez, G., Ngo, L., Gui, C.Y., Marks, P.A. Cancer Res. (2005) [Pubmed]
  6. Biomarker modulation following short-term vorinostat in women with newly diagnosed primary breast cancer. Stearns, V., Jacobs, L.K., Fackler, M., Tsangaris, T.N., Rudek, M.A., Higgins, M., Lange, J., Cheng, Z., Slater, S.A., Jeter, S.C., Powers, P., Briest, S., Chao, C., Yoshizawa, C., Sugar, E., Espinoza-Delgado, I., Sukumar, S., Gabrielson, E., Davidson, N.E. Clin. Cancer Res. (2013) [Pubmed]
  7. Phase I Study of Vorinostat as a Radiation Sensitizer with 131I-Metaiodobenzylguanidine (131I-MIBG) for Patients with Relapsed or Refractory Neuroblastoma. DuBois, S.G., Groshen, S., Park, J.R., Haas-Kogan, D.A., Yang, X., Geier, E., Chen, E., Giacomini, K., Weiss, B., Cohn, S.L., Granger, M.M., Yanik, G.A., Hawkins, R., Courtier, J., Jackson, H., Goodarzian, F., Shimada, H., Czarnecki, S., Tsao-Wei, D., Villablanca, J.G., Marachelian, A., Matthay, K.K. Clin. Cancer Res. (2015) [Pubmed]
  8. Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in a mouse model of Huntington's disease. Hockly, E., Richon, V.M., Woodman, B., Smith, D.L., Zhou, X., Rosa, E., Sathasivam, K., Ghazi-Noori, S., Mahal, A., Lowden, P.A., Steffan, J.S., Marsh, J.L., Thompson, L.M., Lewis, C.M., Marks, P.A., Bates, G.P. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  9. Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors. Finnin, M.S., Donigian, J.R., Cohen, A., Richon, V.M., Rifkind, R.A., Marks, P.A., Breslow, R., Pavletich, N.P. Nature (1999) [Pubmed]
  10. Histone deacetylase inhibitors: inducers of differentiation or apoptosis of transformed cells. Marks, P.A., Richon, V.M., Rifkind, R.A. J. Natl. Cancer Inst. (2000) [Pubmed]
  11. Identification and functional significance of genes regulated by structurally different histone deacetylase inhibitors. Peart, M.J., Smyth, G.K., van Laar, R.K., Bowtell, D.D., Richon, V.M., Marks, P.A., Holloway, A.J., Johnstone, R.W. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  12. Role of thioredoxin in the response of normal and transformed cells to histone deacetylase inhibitors. Ungerstedt, J.S., Sowa, Y., Xu, W.S., Shao, Y., Dokmanovic, M., Perez, G., Ngo, L., Holmgren, A., Jiang, X., Marks, P.A. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  13. Synergistic induction of oxidative injury and apoptosis in human multiple myeloma cells by the proteasome inhibitor bortezomib and histone deacetylase inhibitors. Pei, X.Y., Dai, Y., Grant, S. Clin. Cancer Res. (2004) [Pubmed]
  14. Cotreatment with Vorinostat (Suberoylanilide Hydroxamic Acid) Enhances Activity of Dasatinib (BMS-354825) against Imatinib Mesylate-Sensitive or Imatinib Mesylate-Resistant Chronic Myelogenous Leukemia Cells. Fiskus, W., Pranpat, M., Balasis, M., Bali, P., Estrella, V., Kumaraswamy, S., Rao, R., Rocha, K., Herger, B., Lee, F., Richon, V., Bhalla, K. Clin. Cancer Res. (2006) [Pubmed]
  15. The histone deacetylase inhibitor suberoylanilide hydroxamic Acid induces growth inhibition and enhances gemcitabine-induced cell death in pancreatic cancer. Arnold, N.B., Arkus, N., Gunn, J., Korc, M. Clin. Cancer Res. (2007) [Pubmed]
  16. In vitro and ex vivo evaluation of second-generation histone deacetylase inhibitors for the treatment of spinal muscular atrophy. Hahnen, E., Eyüpoglu, I.Y., Brichta, L., Haastert, K., Tränkle, C., Siebzehnrübl, F.A., Riessland, M., Hölker, I., Claus, P., Romstöck, J., Buslei, R., Wirth, B., Blümcke, I. J. Neurochem. (2006) [Pubmed]
  17. Will broad-spectrum histone deacetylase inhibitors be superseded by more specific compounds? Karagiannis, T.C., El-Osta, A. Leukemia (2007) [Pubmed]
  18. Histone deacetylase (HDAC) inhibitor activation of p21WAF1 involves changes in promoter-associated proteins, including HDAC1. Gui, C.Y., Ngo, L., Xu, W.S., Richon, V.M., Marks, P.A. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  19. Apoptotic and autophagic cell death induced by histone deacetylase inhibitors. Shao, Y., Gao, Z., Marks, P.A., Jiang, X. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  20. Molecular sequelae of histone deacetylase inhibition in human malignant B cells. Mitsiades, N., Mitsiades, C.S., Richardson, P.G., McMullan, C., Poulaki, V., Fanourakis, G., Schlossman, R., Chauhan, D., Munshi, N.C., Hideshima, T., Richon, V.M., Marks, P.A., Anderson, K.C. Blood (2003) [Pubmed]
  21. Histone deacetylase inhibitors suppress the inducibility of nuclear factor-kappaB by tumor necrosis factor-alpha receptor-1 down-regulation. Imre, G., Gekeler, V., Leja, A., Beckers, T., Boehm, M. Cancer Res. (2006) [Pubmed]
  22. Coadministration of the heat shock protein 90 antagonist 17-allylamino- 17-demethoxygeldanamycin with suberoylanilide hydroxamic acid or sodium butyrate synergistically induces apoptosis in human leukemia cells. Rahmani, M., Yu, C., Dai, Y., Reese, E., Ahmed, W., Dent, P., Grant, S. Cancer Res. (2003) [Pubmed]
  23. Photoaffinity labeling and mass spectrometry identify ribosomal protein S3 as a potential target for hybrid polar cytodifferentiation agents. Webb, Y., Zhou, X., Ngo, L., Cornish, V., Stahl, J., Erdjument-Bromage, H., Tempst, P., Rifkind, R.A., Marks, P.A., Breslow, R., Richon, V.M. J. Biol. Chem. (1999) [Pubmed]
  24. Cotreatment with the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) enhances imatinib-induced apoptosis of Bcr-Abl-positive human acute leukemia cells. Nimmanapalli, R., Fuino, L., Stobaugh, C., Richon, V., Bhalla, K. Blood (2003) [Pubmed]
  25. Antileukemia activity of the combination of an anthracycline with a histone deacetylase inhibitor. Sanchez-Gonzalez, B., Yang, H., Bueso-Ramos, C., Hoshino, K., Quintas-Cardama, A., Richon, V.M., Garcia-Manero, G. Blood (2006) [Pubmed]
  26. Coadministration of histone deacetylase inhibitors and perifosine synergistically induces apoptosis in human leukemia cells through Akt and ERK1/2 inactivation and the generation of ceramide and reactive oxygen species. Rahmani, M., Reese, E., Dai, Y., Bauer, C., Payne, S.G., Dent, P., Spiegel, S., Grant, S. Cancer Res. (2005) [Pubmed]
  27. Histone deacetylase inhibitors suppress the induction of c-Jun and its target genes including COX-2. Yamaguchi, K., Lantowski, A., Dannenberg, A.J., Subbaramaiah, K. J. Biol. Chem. (2005) [Pubmed]
  28. Histone deacetylase inhibitors induce growth suppression and cell death in human rhabdomyosarcoma in vitro. Kutko, M.C., Glick, R.D., Butler, L.M., Coffey, D.C., Rifkind, R.A., Marks, P.A., Richon, V.M., LaQuaglia, M.P. Clin. Cancer Res. (2003) [Pubmed]
  29. Phase I and pharmacokinetic study of vorinostat, a histone deacetylase inhibitor, in combination with carboplatin and paclitaxel for advanced solid malignancies. Ramalingam, S.S., Parise, R.A., Ramanathan, R.K., Ramananthan, R.K., Lagattuta, T.F., Musguire, L.A., Stoller, R.G., Potter, D.M., Argiris, A.E., Zwiebel, J.A., Egorin, M.J., Belani, C.P. Clin. Cancer Res. (2007) [Pubmed]
  30. Preclinical studies of vorinostat (suberoylanilide hydroxamic acid) combined with cytosine arabinoside and etoposide for treatment of acute leukemias. Shiozawa, K., Nakanishi, T., Tan, M., Fang, H.B., Wang, W.C., Edelman, M.J., Carlton, D., Gojo, I., Sausville, E.A., Ross, D.D. Clin. Cancer Res. (2009) [Pubmed]
  31. A phase I, pharmacokinetic, and pharmacodynamic study of two schedules of vorinostat in combination with 5-fluorouracil and leucovorin in patients with refractory solid tumors. Fakih, M.G., Fetterly, G., Egorin, M.J., Muindi, J.R., Espinoza-Delgado, I., Zwiebel, J.A., Litwin, A., Holleran, J.L., Wang, K., Diasio, R.B. Clin. Cancer Res. (2010) [Pubmed]
  32. Phase I study of vorinostat in combination with temozolomide in patients with high-grade gliomas: North American Brain Tumor Consortium Study 04-03. Lee, E.Q., Puduvalli, V.K., Reid, J.M., Kuhn, J.G., Lamborn, K.R., Cloughesy, T.F., Chang, S.M., Drappatz, J., Yung, W.K., Gilbert, M.R., Robins, H.I., Lieberman, F.S., Lassman, A.B., McGovern, R.M., Xu, J., Desideri, S., Ye, X., Ames, M.M., Espinoza-Delgado, I., Prados, M.D., Wen, P.Y. Clin. Cancer Res. (2012) [Pubmed]
  33. Translational phase I trial of vorinostat (suberoylanilide hydroxamic acid) combined with cytarabine and etoposide in patients with relapsed, refractory, or high-risk acute myeloid leukemia. Gojo, I., Tan, M., Fang, H.B., Sadowska, M., Lapidus, R., Baer, M.R., Carrier, F., Beumer, J.H., Anyang, B.N., Srivastava, R.K., Espinoza-Delgado, I., Ross, D.D. Clin. Cancer Res. (2013) [Pubmed]
  34. Apoptosis signal-regulating kinase 1 is a direct target of E2F1 and contributes to histone deacetylase inhibitor-induced apoptosis through positive feedback regulation of E2F1 apoptotic activity. Tan, J., Zhuang, L., Jiang, X., Yang, K.K., Karuturi, K.M., Yu, Q. J. Biol. Chem. (2006) [Pubmed]
  35. Importin alpha1 (Rch1) mediates nuclear translocation of thioredoxin-binding protein-2/vitamin D(3)-up-regulated protein 1. Nishinaka, Y., Masutani, H., Oka, S., Matsuo, Y., Yamaguchi, Y., Nishio, K., Ishii, Y., Yodoi, J. J. Biol. Chem. (2004) [Pubmed]
  36. Requirement of histone deacetylase activity for signaling by STAT1. Klampfer, L., Huang, J., Swaby, L.A., Augenlicht, L. J. Biol. Chem. (2004) [Pubmed]
  37. Activation of the p21WAF1/CIP1 promoter independent of p53 by the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) through the Sp1 sites. Huang, L., Sowa, Y., Sakai, T., Pardee, A.B. Oncogene (2000) [Pubmed]
  38. A phase I, pharmacokinetic and pharmacodynamic study on vorinostat in combination with 5-fluorouracil, leucovorin, and oxaliplatin in patients with refractory colorectal cancer. Fakih, M.G., Pendyala, L., Fetterly, G., Toth, K., Zwiebel, J.A., Espinoza-Delgado, I., Litwin, A., Rustum, Y.M., Ross, M.E., Holleran, J.L., Egorin, M.J. Clin. Cancer Res. (2009) [Pubmed]
  39. The histone deacetylase inhibitor SAHA arrests cancer cell growth, up-regulates thioredoxin-binding protein-2, and down-regulates thioredoxin. Butler, L.M., Zhou, X., Xu, W.S., Scher, H.I., Rifkind, R.A., Marks, P.A., Richon, V.M. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  40. Histone deacetylase inhibitor selectively induces p21WAF1 expression and gene-associated histone acetylation. Richon, V.M., Sandhoff, T.W., Rifkind, R.A., Marks, P.A. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  41. Antitumor effects of a novel phenylbutyrate-based histone deacetylase inhibitor, (S)-HDAC-42, in prostate cancer. Kulp, S.K., Chen, C.S., Wang, D.S., Chen, C.Y., Chen, C.S. Clin. Cancer Res. (2006) [Pubmed]
  42. Selective induction of apoptosis by histone deacetylase inhibitor SAHA in cutaneous T-cell lymphoma cells: relevance to mechanism of therapeutic action. Zhang, C., Richon, V., Ni, X., Talpur, R., Duvic, M. J. Invest. Dermatol. (2005) [Pubmed]
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