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Chemical Compound Review

Herbimycin     [(8R,9R,12S,13R,14S,16S,17S)- 8,13,14,17...

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Disease relevance of Herbimycin


High impact information on Herbimycin


Chemical compound and disease context of Herbimycin


Biological context of Herbimycin

  • IK currents are markedly downregulated upon exposure of cells to the tyrosine kinase inhibitors herbimycin A and genistein, while a potent upregulation of IK is observed when recombinant Fyn kinase is introduced through the patch pipette [13].
  • Experiments with non-myristylation and temperature-sensitive mutants of RSV and with herbimycin A, a potent inhibitor of tyrosine kinases, suggest that both the suppression of cell adhesion and tyrosine phosphorylation of catenins are highly transformation-specific [14].
  • Treatment of cells with tyrosine kinase inhibitors (genistein, 10 micrograms/ml or herbimycin A, 0.5 micrograms/ml) or microinjection of anti-phosphotyrosine antibodies inhibited the transient protein tyrosine phosphorylation in response to HA as well as prevented HA stimulation of cell motility [15].
  • Integrin beta-chain (CD18) crosslinking independently induced downstream mobilization of intracellular Ca2+ and potently costimulated TCR-induced Ca2+ flux with an increase in both amplitude and kinetics. beta 2-Integrin signaling through this pathway was completely inhibited by herbimycin A and was prevented by TCR modulation [16].
  • Pretreatment of cloned T cells, but not APCs, with herbimycin A resulted in complete inhibition of triggering events, indicating that the acidification response is mediated by T-cell second messenger pathways [17].

Anatomical context of Herbimycin


Associations of Herbimycin with other chemical compounds


Gene context of Herbimycin

  • Inhibition of tyrosine phosphorylation, by herbimycin A, blocked crystal-induced COX-2 [27].
  • An immunocomplex kinase assay showed that both IFN-gamma and TPA activated c-Src and Lyn activities and that these effects were inhibited by staurosporine and herbimycin [28].
  • IKK activity was stimulated by both TNF-alpha and TPA, and these effects were inhibited by staurosporine or herbimycin [29].
  • Inhibition of PTKs by herbimycin A completely blocks LPS-induced down-modulation of CD14 and production of TNF-alpha and IL-1 [30].
  • Stretch-induced activation of ERK was inhibited by herbimycin A, a tyrosine kinase inhibitor, but not by GF109203X or calphostin C, the inhibitors of protein kinase C. Mechanical stretch also enhanced DNA-binding activity of AP-1, and this enhancement was inhibited by PD98059, an inhibitor of MAPK or ERK kinase (MEK) [31].

Analytical, diagnostic and therapeutic context of Herbimycin


  1. Use of chemokine receptors by poxviruses. Lalani, A.S., Masters, J., Zeng, W., Barrett, J., Pannu, R., Everett, H., Arendt, C.W., McFadden, G. Science (1999) [Pubmed]
  2. Herbimycin A, a pp60c-src tyrosine kinase inhibitor, inhibits osteoclastic bone resorption in vitro and hypercalcemia in vivo. Yoneda, T., Lowe, C., Lee, C.H., Gutierrez, G., Niewolna, M., Williams, P.J., Izbicka, E., Uehara, Y., Mundy, G.R. J. Clin. Invest. (1993) [Pubmed]
  3. Induction of in vitro differentiation of mouse embryonal carcinoma (F9) and erythroleukemia (MEL) cells by herbimycin A, an inhibitor of protein phosphorylation. Kondo, K., Watanabe, T., Sasaki, H., Uehara, Y., Oishi, M. J. Cell Biol. (1989) [Pubmed]
  4. Participation of tyrosine phosphorylation in the cytopathic effect of human immunodeficiency virus-1. Cohen, D.I., Tani, Y., Tian, H., Boone, E., Samelson, L.E., Lane, H.C. Science (1992) [Pubmed]
  5. Retro-retinoids in regulated cell growth and death. O'Connell, M.J., Chua, R., Hoyos, B., Buck, J., Chen, Y., Derguini, F., Hämmerling, U. J. Exp. Med. (1996) [Pubmed]
  6. Receptor-induced death in human natural killer cells: involvement of CD16. Ortaldo, J.R., Mason, A.T., O'Shea, J.J. J. Exp. Med. (1995) [Pubmed]
  7. CD40 signaling pathway: anti-CD40 monoclonal antibody induces rapid dephosphorylation and phosphorylation of tyrosine-phosphorylated proteins including protein tyrosine kinase Lyn, Fyn, and Syk and the appearance of a 28-kD tyrosine phosphorylated protein. Faris, M., Gaskin, F., Parsons, J.T., Fu, S.M. J. Exp. Med. (1994) [Pubmed]
  8. Mitogen-activated protein kinase (ERK1/2) activation by shear stress and adhesion in endothelial cells. Essential role for a herbimycin-sensitive kinase. Takahashi, M., Berk, B.C. J. Clin. Invest. (1996) [Pubmed]
  9. Geldanamycin and herbimycin A induce apoptotic killing of B chronic lymphocytic leukemia cells and augment the cells' sensitivity to cytotoxic drugs. Jones, D.T., Addison, E., North, J.M., Lowdell, M.W., Hoffbrand, A.V., Mehta, A.B., Ganeshaguru, K., Folarin, N.I., Wickremasinghe, R.G. Blood (2004) [Pubmed]
  10. Diverging signal transduction pathways activated by interleukin-8 and related chemokines in human neutrophils: interleukin-8, but not NAP-2 or GRO alpha, stimulates phospholipase D activity. L'Heureux, G.P., Bourgoin, S., Jean, N., McColl, S.R., Naccache, P.H. Blood (1995) [Pubmed]
  11. FLT3 expressing leukemias are selectively sensitive to inhibitors of the molecular chaperone heat shock protein 90 through destabilization of signal transduction-associated kinases. Yao, Q., Nishiuchi, R., Li, Q., Kumar, A.R., Hudson, W.A., Kersey, J.H. Clin. Cancer Res. (2003) [Pubmed]
  12. Protein kinase Cs and tyrosine kinases in permissive action of prostacyclin on cerebrovascular regulation in newborn pigs. Rama, G.P., Parfenova, H., Leffler, C.W. Pediatr. Res. (1997) [Pubmed]
  13. Constitutive activation of delayed-rectifier potassium channels by a src family tyrosine kinase in Schwann cells. Sobko, A., Peretz, A., Attali, B. EMBO J. (1998) [Pubmed]
  14. p60v-src causes tyrosine phosphorylation and inactivation of the N-cadherin-catenin cell adhesion system. Hamaguchi, M., Matsuyoshi, N., Ohnishi, Y., Gotoh, B., Takeichi, M., Nagai, Y. EMBO J. (1993) [Pubmed]
  15. Hyaluronan and the hyaluronan receptor RHAMM promote focal adhesion turnover and transient tyrosine kinase activity. Hall, C.L., Wang, C., Lange, L.A., Turley, E.A. J. Cell Biol. (1994) [Pubmed]
  16. Beta 2-integrin LFA-1 signaling through phospholipase C-gamma 1 activation. Kanner, S.B., Grosmaire, L.S., Ledbetter, J.A., Damle, N.K. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  17. Stimulation of T cells by antigen-presenting cells is kinetically controlled by antigenic peptide binding to major histocompatibility complex class II molecules. McConnell, H.M., Wada, H.G., Arimilli, S., Fok, K.S., Nag, B. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  18. Tyrosine kinase is required for long-term depression in the cerebellum. Boxall, A.R., Lancaster, B., Garthwaite, J. Neuron (1996) [Pubmed]
  19. Mitochondrial proliferation and paradoxical membrane depolarization during terminal differentiation and apoptosis in a human colon carcinoma cell line. Mancini, M., Anderson, B.O., Caldwell, E., Sedghinasab, M., Paty, P.B., Hockenbery, D.M. J. Cell Biol. (1997) [Pubmed]
  20. Inhibition of tyrosine phosphorylation prevents T-cell receptor-mediated signal transduction. June, C.H., Fletcher, M.C., Ledbetter, J.A., Schieven, G.L., Siegel, J.N., Phillips, A.F., Samelson, L.E. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  21. Tyrosine phosphorylation provides an early and requisite signal for the activation of natural killer cell cytotoxic function. Einspahr, K.J., Abraham, R.T., Binstadt, B.A., Uehara, Y., Leibson, P.J. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  22. Stimulation of beta1 integrins on fibroblasts induces PDGF independent tyrosine phosphorylation of PDGF beta-receptors. Sundberg, C., Rubin, K. J. Cell Biol. (1996) [Pubmed]
  23. Ceramide-induced inhibition of T lymphocyte voltage-gated potassium channel is mediated by tyrosine kinases. Gulbins, E., Szabo, I., Baltzer, K., Lang, F. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  24. Transient and prolonged increase in endothelial permeability induced by histamine and thrombin: role of protein kinases, calcium, and RhoA. van Nieuw Amerongen, G.P., Draijer, R., Vermeer, M.A., van Hinsbergh, V.W. Circ. Res. (1998) [Pubmed]
  25. Benzoquinonoid ansamycins possess selective tumoricidal activity unrelated to src kinase inhibition. Whitesell, L., Shifrin, S.D., Schwab, G., Neckers, L.M. Cancer Res. (1992) [Pubmed]
  26. Bcr-Abl-mediated resistance to apoptosis is independent of constant tyrosine-kinase activity. Bueno-da-Silva, A.E., Brumatti, G., Russo, F.O., Green, D.R., Amarante-Mendes, G.P. Cell Death Differ. (2003) [Pubmed]
  27. Monosodium urate microcrystals induce cyclooxygenase-2 in human monocytes. Pouliot, M., James, M.J., McColl, S.R., Naccache, P.H., Cleland, L.G. Blood (1998) [Pubmed]
  28. Interferon-gamma-induced epithelial ICAM-1 expression and monocyte adhesion. Involvement of protein kinase C-dependent c-Src tyrosine kinase activation pathway. Chang, Y.J., Holtzman, M.J., Chen, C.C. J. Biol. Chem. (2002) [Pubmed]
  29. TNF-alpha-induced cyclooxygenase-2 expression in human lung epithelial cells: involvement of the phospholipase C-gamma 2, protein kinase C-alpha, tyrosine kinase, NF-kappa B-inducing kinase, and I-kappa B kinase 1/2 pathway. Chen, C.C., Sun, Y.T., Chen, J.J., Chiu, K.T. J. Immunol. (2000) [Pubmed]
  30. Lipopolysaccharide induces activation of CD14-associated protein tyrosine kinase p53/56lyn. Stefanová, I., Corcoran, M.L., Horak, E.M., Wahl, L.M., Bolen, J.B., Horak, I.D. J. Biol. Chem. (1993) [Pubmed]
  31. Stretch-induced overproduction of fibronectin in mesangial cells is mediated by the activation of mitogen-activated protein kinase. Ishida, T., Haneda, M., Maeda, S., Koya, D., Kikkawa, R. Diabetes (1999) [Pubmed]
  32. Characterization of the M(r) 65,000 lymphokine-activated killer proteins phosphorylated after tumor target binding: evidence that pp65a and pp65b are phosphorylated forms of L-plastin. Frederick, M.J., Rodriguez, L.V., Johnston, D.A., Darnay, B.G., Grimm, E.A. Cancer Res. (1996) [Pubmed]
  33. Fc gamma receptor signal transduction in natural killer cells. Coupling to phospholipase C via a G protein-independent, but tyrosine kinase-dependent pathway. Ting, A.T., Einspahr, K.J., Abraham, R.T., Leibson, P.J. J. Immunol. (1991) [Pubmed]
  34. Tyrosine protein kinase is involved in anti-IgM-mediated signaling in BAL17 B lymphoma cells. Mizuguchi, J., Yamanashi, Y., Ehara, K., Tamura, T., Nariuchi, H., Gyotoku, Y., Fukazawa, H., Uehara, Y., Yamamoto, T. J. Immunol. (1992) [Pubmed]
  35. Effect of herbimycin A on growth and pp60c-src activity in human colon tumor cell lines. Garcia, R., Parikh, N.U., Saya, H., Gallick, G.E. Oncogene (1991) [Pubmed]
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