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Chemical Compound Review

SureCN3764335     4-[2-[(1S,3S,5S)-3,5- dimethyl-2-oxo...

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Disease relevance of cycloheximide


High impact information on cycloheximide

  • The incubation of OKT8(-) T cells with LTB4 for 18 h resulted in the appearance of the OKT8(+) on 10-20% of the cells, and this could be blocked by cyclohexamide but not by mitomycin C [6].
  • This LTB4-induced suppressor cell was radiosensitive, and its generation could be blocked by cyclohexamide but not by mitomycin C [6].
  • The inability of cyclohexamide treatment to effect the TGR localization of GLUT-4 indicates that GLUT-4 enters the ANF secretory granules at the TGR via the recycling pathway and not via the biosynthetic pathway [7].
  • The inhibitory effect of 1,25(OH)2D3 on erythroid differentiation of K562 cells was abrogated by cyclohexamide (20 micrograms/mL), an inhibitor of protein synthesis [8].
  • We also performed studies on lymphocytes cultured in the presence of cyclohexamide, which suggested that the expression of class I HLA antigens and B2 microglobulin are highly sensitive to the inhibition of protein synthesis, whereas the expression of class II HLA antigens, Leu-4, and HLe-1 are not [9].

Chemical compound and disease context of cycloheximide


Biological context of cycloheximide

  • In addition, cyclohexamide treatment was found to markedly increase the stability of pim-1 transcripts in bovine PBMC suggesting that a protein synthesis-dependent posttranscriptional pim-1 mRNA degradation pathway may be involved in the regulation of pim-1 mRNA levels in lymphoid cells [11].
  • Quantitation of the levels of the BEF-1 isoforms, and studies in the presence of cyclohexamide, provided evidence for the phosphorylation of an existing intracellular pool of BEF-1, with no change in the total intracellular level [12].
  • This detection of CD80 is attributable to the acquisition of CD80 from APCs, as opposed to the up-regulation of endogenous CD80, as demonstrated by CD4(+) T cells treated with cyclohexamide [13].
  • RNA expression experiments with transgenic tobacco seedlings or with transfected pea protoplasts using PS-IAA4/5 promoter GUS or CAT fusions reveal that CHX transcriptionally activates PS-IAA4/5 gene expression [14].
  • The inducibility of DNA synthesis after treatment with cyclohexamide (CHM) during mitosis and the G1 phase of WI38 cells has been studied in the heterokaryons following fusion with HeLa cells in S phase [15].

Anatomical context of cycloheximide

  • Inhibitors of microtubules (colchicine and vinca alkaloids) and of protein synthesis (cyclohexamide) had no effect [16].
  • This priming by LPS is dependent on protein synthesis, given that cyclohexamide blocks the ability of LPS to prime macrophages for activation of caspase-1 by the P2X7R [17].
  • In this study human fibroblast monolayers that were incubated with cyclohexamide (50 micrograms/ml) for 14 h at 37 C had no detectable 35 K protein on their cell surface, but type I Sm-C/IGF-I receptors were still present [18].
  • Effects of cyclohexamide on a cytoplasmic factor initiating meiotic naturation in Xenopus oocytes [19].
  • In explant cultures, Bmp activation of Odd-skipped related 1 (Odd-1), the earliest known gene expressed in the intermediate mesoderm, is blocked by cyclohexamide, indicating that the activation of Odd-1 by Bmp signaling is translation-dependent [20].

Associations of cycloheximide with other chemical compounds


Gene context of cycloheximide

  • Experiments with cyclohexamide-dependent block of protein synthesis showed that the half-life of CUGBP1 is increased in cells expressing CUG repeats [25].
  • The induction of BRCA1 mRNA was blocked by cyclohexamide [26].
  • It is interesting that activation of these signaling molecules by G-CSF was prolonged by pretreating cells with actinomycin D or cyclohexamide, suggesting that de novo protein synthesis is required for appropriate termination of G-CSF-R signaling [27].
  • These BR isoforms were activated by 20E in fat bodies cultured in vitro and behaved as early genes, with a self-repressive autoregulatory loop that can be blocked by the protein inhibitor, cyclohexamide [28].
  • Inhibitor studies revealed no significant difference among control, cyclohexamide, and actinomycin D supernatants for tPA, suggesting release of protein rather than active synthesis [29].

Analytical, diagnostic and therapeutic context of cycloheximide

  • Analysis of poly(A+)RNA by northern blots revealed hybridization of an IGF-I cDNA to a 7.5- to 7.0-kb transcript and superinduction of the 7.5-7.0-kb mRNA by the translational inhibitor, cyclohexamide [30].
  • Western blot analysis showed that IFN-tau and CHX treatment resulted in a greater expression of the proapoptotic protein Bax-alpha compared with that in control cultures [31].
  • 6. RT-PCR revealed elevated iNOS mRNA levels after 12 h of exposure to CH [32].
  • Cyclohexamide did not affect rosette formation, suggesting that agglutinins may be preformed and stored in leukocytes prior to secretion [33].
  • Immunoprecipitation of NR1 following the block of protein synthesis by cyclohexamide revealed that the rapidly and slowly degrading pools mainly consisted of the NR1 splice variants NR1-4a and NR1-2a [34].


  1. Involvement of a ferroprotein sensor in hypoxia-mediated inhibition of neutrophil apoptosis. Mecklenburgh, K.I., Walmsley, S.R., Cowburn, A.S., Wiesener, M., Reed, B.J., Upton, P.D., Deighton, J., Greening, A.P., Chilvers, E.R. Blood (2002) [Pubmed]
  2. Induction of intercellular adhesion molecule 1 on primary and continuous cell lines by pro-inflammatory cytokines. Regulation by pharmacologic agents and neutralizing antibodies. Rothlein, R., Czajkowski, M., O'Neill, M.M., Marlin, S.D., Mainolfi, E., Merluzzi, V.J. J. Immunol. (1988) [Pubmed]
  3. Transcriptional activation of the human immunodeficiency virus type 1 long terminal repeat by hepatitis B virus X-protein requires de novo protein synthesis. Twu, J.S., Wu, J.Y., Robinson, W.S. Virology (1990) [Pubmed]
  4. Partial elimination of latent Epstein-Barr virus genomes from virus-producing cells by cyclohexamide. Tanaka, A., Nonoyama, M., Hampar, B. Virology (1976) [Pubmed]
  5. Modulation of fas-mediated apoptosis in osteosarcoma cell lines. Hamada, T., Komiya, S., Yano, H., Zenmyo, M., Hiraoka, K., Inoue, A., Morimatsu, M. Int. J. Oncol. (1999) [Pubmed]
  6. Control of polyclonal immunoglobulin production from human lymphocytes by leukotrienes; leukotriene B4 induces an OKT8(+), radiosensitive suppressor cell from resting, human OKT8(-) T cells. Atluru, D., Goodwin, J.S. J. Clin. Invest. (1984) [Pubmed]
  7. Glucose transporter (GLUT-4) is targeted to secretory granules in rat atrial cardiomyocytes. Slot, J.W., Garruti, G., Martin, S., Oorschot, V., Posthuma, G., Kraegen, E.W., Laybutt, R., Thibault, G., James, D.E. J. Cell Biol. (1997) [Pubmed]
  8. Inhibition by 1,25 dihydroxyvitamin D3 of chemically induced erythroid differentiation of K562 leukemia cells. Moore, D.C., Carter, D.L., Bhandal, A.K., Studzinski, G.P. Blood (1991) [Pubmed]
  9. Stability of antigens on leukocytes in banked platelet concentrates: decline in HLA-DR antigen expression and mixed lymphocyte culture stimulating capacity following storage. Sherman, M.E., Dzik, W.H. Blood (1988) [Pubmed]
  10. Studies on fatty liver with isolated hepatocytes. I. The action of colchicine, phalloidin, cytochalasin B, and cyclohexamide on protein and triglyceride synthesis and secretion. Gravela, E., Poli, G., Albano, E., Dianzani, M.U. Exp. Mol. Pathol. (1977) [Pubmed]
  11. Stability changes in pim-1 proto-oncogene mRNA after mitogen stimulation of normal lymphocytes. Wingett, D., Reeves, R., Magnuson, N.S. J. Immunol. (1991) [Pubmed]
  12. Trans-repressor BEF-1 phosphorylation. A potential control mechanism for human ApoE gene regulation. Berg, D.T., Calnek, D.S., Grinnell, B.W. J. Biol. Chem. (1996) [Pubmed]
  13. Acquisition of CD80 by human T cells at early stages of activation: functional involvement of CD80 acquisition in T cell to T cell interaction. Tatari-Calderone, Z., Semnani, R.T., Nutman, T.B., Schlom, J., Sabzevari, H. J. Immunol. (2002) [Pubmed]
  14. Transcriptional regulation of PS-IAA4/5 and PS-IAA6 early gene expression by indoleacetic acid and protein synthesis inhibitors in pea (Pisum sativum). Koshiba, T., Ballas, N., Wong, L.M., Theologis, A. J. Mol. Biol. (1995) [Pubmed]
  15. Differences in the response of early and mid or late G1 WI38 cells treated with cyclohexamide to HeLa inducers of DNA synthesis. Rao, M.V. Exp. Cell Res. (1987) [Pubmed]
  16. Influence of inhibitors of cellular function on chemotactic factor-induced neutrophil aggregation. O'Flaherty, J.T., Kreutzer, D.L., Showell, H.J., Ward, P.A. J. Immunol. (1977) [Pubmed]
  17. Potentiation of caspase-1 activation by the P2X7 receptor is dependent on TLR signals and requires NF-kappaB-driven protein synthesis. Kahlenberg, J.M., Lundberg, K.C., Kertesy, S.B., Qu, Y., Dubyak, G.R. J. Immunol. (2005) [Pubmed]
  18. Alterations in the synthesis of a fibroblast surface associated 35 K protein modulates the binding of somatomedin-C/insulin-like growth factor I. Clemmons, D.R., Han, V.K., Elgin, R.G., D'Ercole, A.J. Mol. Endocrinol. (1987) [Pubmed]
  19. Effects of cyclohexamide on a cytoplasmic factor initiating meiotic naturation in Xenopus oocytes. Wasserman, W.J., Masui, Y. Exp. Cell Res. (1975) [Pubmed]
  20. Bmp signaling promotes intermediate mesoderm gene expression in a dose-dependent, cell-autonomous and translation-dependent manner. James, R.G., Schultheiss, T.M. Dev. Biol. (2005) [Pubmed]
  21. Elevated D-glucose concentrations modulate TGF-beta 1 synthesis by human cultured renal proximal tubular cells. The permissive role of platelet-derived growth factor. Phillips, A.O., Steadman, R., Topley, N., Williams, J.D. Am. J. Pathol. (1995) [Pubmed]
  22. Roles for interleukin-1beta, phorbol ester and a post-transcriptional regulator in the control of bradykinin B1 receptor gene expression. Zhou, X., Polgar, P., Taylor, L. Biochem. J. (1998) [Pubmed]
  23. Growth state-dependent regulation of plasminogen activator inhibitor type-1 gene expression during epithelial cell stimulation by serum and transforming growth factor-beta1. Boehm, J.R., Kutz, S.M., Sage, E.H., Staiano-Coico, L., Higgins, P.J. J. Cell. Physiol. (1999) [Pubmed]
  24. HIV-1 gp120-induced TNF-{alpha} production by primary human macrophages is mediated by phosphatidylinositol-3 (PI-3) kinase and mitogen-activated protein (MAP) kinase pathways. Lee, C., Tomkowicz, B., Freedman, B.D., Collman, R.G. J. Leukoc. Biol. (2005) [Pubmed]
  25. RNA CUG repeats sequester CUGBP1 and alter protein levels and activity of CUGBP1. Timchenko, N.A., Cai, Z.J., Welm, A.L., Reddy, S., Ashizawa, T., Timchenko, L.T. J. Biol. Chem. (2001) [Pubmed]
  26. The anti-proliferative effects of 1alpha,25(OH)2D3 on breast and prostate cancer cells are associated with induction of BRCA1 gene expression. Campbell, M.J., Gombart, A.F., Kwok, S.H., Park, S., Koeffler, H.P. Oncogene (2000) [Pubmed]
  27. Tyrosine 729 of the G-CSF receptor controls the duration of receptor signaling: involvement of SOCS3 and SOCS1. Zhuang, D., Qiu, Y., Haque, S.J., Dong, F. J. Leukoc. Biol. (2005) [Pubmed]
  28. The early gene Broad is involved in the ecdysteroid hierarchy governing vitellogenesis of the mosquito Aedes aegypti. Chen, L., Zhu, J., Sun, G., Raikhel, A.S. J. Mol. Endocrinol. (2004) [Pubmed]
  29. Plasminogen activator levels are influenced by location and varicosity in greater saphenous vein. Shireman, P.K., McCarthy, W.J., Pearce, W.H., Shively, V.P., Cipollone, M., Kwaan, H.C., Yao, J.S. J. Vasc. Surg. (1996) [Pubmed]
  30. Sequestration and secretion of insulin-like growth factor-I by bovine aortic endothelial cells. Gajdusek, C.M., Luo, Z., Mayberg, M.R. J. Cell. Physiol. (1993) [Pubmed]
  31. Progesterone-modulated induction of apoptosis by interferon-tau in cultured epithelial cells of bovine endometrium. Wang, B., Xiao, C., Goff, A.K. Biol. Reprod. (2003) [Pubmed]
  32. Induction of nitric oxide synthase by protein synthesis inhibition in aortic smooth muscle cells. Marczin, N., Go, C.Y., Papapetropoulos, A., Catravas, J.D. Br. J. Pharmacol. (1998) [Pubmed]
  33. In vitro agglutinin production by earthworm leukocytes. Stein, E.A., Cooper, E.L. Dev. Comp. Immunol. (1988) [Pubmed]
  34. Turnover analysis of N-methyl-D-aspartate receptor subunit NR1 protein in PC12 cells. Vazhappilly, R., Sucher, N.J. Neurosci. Lett. (2002) [Pubmed]
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