Signal-transduction cascades as targets for therapeutic intervention by natural products
Abstract
Many bacteria and fungi produce natural products that are toxic to other microorganisms and have a variety of physiological effects in animals. Recent studies have revealed that, in several cases, the targets of these agents are components of conserved signal-transduction cascades. This article looks at the mechanisms of action of five natural products--the immunosuppressants cyclosporin A, FK506 and rapamycin, and the antiproliferative agents wortmannin and geldanamycin. These mechanisms reveal the importance of signal-transduction cascades as targets for therapeutic intervention and the enormous utility of studies of natural-product action in simple model genetic systems.
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Geldanamycin inhibits heat shock protein HSP90.
“Geldanamycin is a natural fermentation product of the benzoquinone ansamycin and inhibits the heat shock protein HSP90 [220], as well show cytotoxic effect against HeLa cells [221].”
From Marine Natural Products: A Source of Novel Anticancer Drugs (2019) · cites this paper as [220]
Cites
Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery
Datta, S. R., Dudek, H., Tao, X., Masters, S., Fu, H., Gotoh, Y., & Greenberg, M. E. (1997) · Cell · doi:10.1016/s0092-8674(00)80405-5 · Cited by 5,689 · see citing works
Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes
Liu, J., Farmer, J. D., Lane, W. S., Friedman, J., Weissman, I., & Schreiber, S. L. (1991) · Cell · doi:10.1016/0092-8674(91)90124-h · Cited by 4,116 · see citing works
TRANSCRIPTION FACTORS OF THE NFAT FAMILY:Regulation and Function
Rao, A., Luo, C. H., & Hogan, P. G. (1997) · Annual Review of Immunology · doi:10.1146/annurev.immunol.15.1.707 · Cited by 2,592 · see citing works
The mechanism of action of cyclosporin A and FK506
Schreiber, S. L., & Crabtree, G. R. (1992) · Immunology Today · doi:10.1016/0167-5699(92)90111-j · Cited by 2,127 · see citing works
A mammalian protein targeted by G1-arresting rapamycin–receptor complex
Brown, E. J., Albers, M. W., Bum Shin, T., ichikawa, K., Keith, C. T., Lane, W. S., & Schreiber, S. L. (1994) · Nature · doi:10.1038/369756a0 · Cited by 2,053 · see citing works
Targets for Cell Cycle Arrest by the Immunosuppressant Rapamycin in Yeast
Heitman, J., Movva, N. R., & Hall, M. N. (1991) · Science · doi:10.1126/science.1715094 · Cited by 2,010 · see citing works
Self-citationPI3K: Downstream AKTion Blocks Apoptosis
Franke, T. F., Kaplan, D. R., & Cantley, L. C. (1997) · Cell · doi:10.1016/s0092-8674(00)81883-8 · Cited by 1,692 · see citing works
Identification of calcineurin as a key signalling enzyme in T-lymphocyte activation
Clipstone, N. A., & Crabtree, G. R. (1992) · Nature · doi:10.1038/357695a0 · Cited by 1,635 · see citing works
Sabatini, D. M., Erdjument-Bromage, H., Lui, M., Tempst, P., & Snyder, S. H. (1994) · Cell · doi:10.1016/0092-8674(94)90570-3 · Cited by 1,509 · see citing works
Whitesell, L., Mimnaugh, E. G., De Costa, B., Myers, C. E., & Neckers, L. M. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.18.8324 · Cited by 1,444 · see citing works
Stebbins, C. E., Russo, A. A., Schneider, C. B., Rosen, N. X., Hartl, F. U., & Pavletich, N. P. (1997) · Cell · doi:10.1016/s0092-8674(00)80203-2 · Cited by 1,370 · see citing works
Cryptococcosis in the era of AIDS--100 years after the discovery of Cryptococcus neoformans
Mitchell, T. G., & Perfect, J. R. (1995) · Clinical Microbiology Reviews · doi:10.1128/cmr.8.4.515 · Cited by 1,213 · see citing works
The PI 3-kinase/Akt signaling pathway delivers an anti-apoptotic signal.Preprint
Kennedy, S. G., Wagner, A. J., Conzen, S. D., Jordán, J., Bellacosa, A., Tsichlis, P. N., & Hay, N. (1997) · Genes & Development · doi:10.1101/gad.11.6.701 · Cited by 1,074 · see citing works
Phosphorylation of the Translational Repressor PHAS-I by the Mammalian Target of Rapamycin
Brunn, G. J., Hudson, C. C., Sekulić, A., Williams, J. M., Hosoi, H., Houghton, P. J., Lawrence, J. C., & Abraham, R. T. (1997) · Science · doi:10.1126/science.277.5322.99 · Cited by 959 · see citing works
Rapamycin suppresses 5′TOP mRNA translation through inhibition of p70s6k
Jefferies, H. B. J., Fumagalli, S., Dennis, P. B., Reinhard, C., Pearson, R. B., & Thomas, G. (1997) · The EMBO Journal · doi:10.1093/emboj/16.12.3693 · Cited by 934 · see citing works
Okada, T., Kawano, Y., Sakakibara, T., Hazeki, O., & Ui, M. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)41901-6 · Cited by 917 · see citing works
Nourse, J. L., Firpo, E. J., Flanagan, W. M., Coats, S., Polyák, K., Lee, M., Massagué, J., Crabtree, G. R., & Roberts, J. M. (1994) · Nature · doi:10.1038/372570a0 · Cited by 889 · see citing works
Isolation of a Protein Target of the FKBP12-Rapamycin Complex in Mammalian Cells
Sabers, C. J., Martin, M. M., Brunn, G. J., Williams, J. M., Dumont, F. J., Wiederrecht, G., & Abraham, R. T. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.2.815 · Cited by 887 · see citing works
FK-506- and CsA-sensitive activation of the interleukin-2 promoter by calcineurin
O’Keefe, S. J., Tamura, J., Kincaid, R. L., Tocci, M. J., & O’Neill, E. A. (1992) · Nature · doi:10.1038/357692a0 · Cited by 841 · see citing works
Kunz, J., Henríquez, R., Schneider, U., Deuter‐Reinhard, M., Movva, N. R., & Hall, M. N. (1993) · Cell · doi:10.1016/0092-8674(93)90144-f · Cited by 838 · see citing works
X-ray structure of calcineurin inhibited by the immunophilin-immunosuppressant FKBP12-FK506 complex
Griffith, J. P., Kim, J. L., Kim, E. E., Sintchak, M. D., Thomson, J. A., Fitzgibbon, M. J., Fleming, M. A., Caron, P. R., Hsiao, K., & Navia, M. A. (1995) · Cell · doi:10.1016/0092-8674(95)90439-5 · Cited by 834 · see citing works
Crystal structures of human calcineurin and the human FKBP12–FK506–calcineurin complex
Kissinger, C. R., Parge, H. E., Knighton, D. R., Lewis, C. T., Pelletier, L. A., Tempczyk, A., Kalish, V. J., Tucker, K. D., Showalter, R. E., Moomaw, E. W., et al. (1995) · Nature · doi:10.1038/378641a0 · Cited by 762 · see citing works
Hartley, K. O., Gell, D. A., Smith, G. C. M., Zhang, H., Divecha, N., Connelly, M. A., Admon, A., Lees‐Miller, S. P., Anderson, C. W., & Jackson, S. P. (1995) · Cell · doi:10.1016/0092-8674(95)90482-4 · Cited by 745 · see citing works
Yano, H., Nakanishi, S., Kimura, K. D., Hanai, N., Saitoh, Y., Fukui, Y., Nonomura, Y., & Matsuda, Y. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)74466-4 · Cited by 725 · see citing works
Brunn, G. J., Williams, J. M., Sabers, C. J., Wiederrecht, G., Lawrence, J. C., & Abraham, R. T. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00911.x · Cited by 715 · see citing works
Control of p70 S6 kinase by kinase activity of FRAP in vivo
Brown, E. J., Beal, P. A., Keith, C. T., Chen, J., Shin, T. B., & Schreiber, S. L. (1995) · Nature · doi:10.1038/377441a0 · Cited by 705 · see citing works
Wymann, M. P., Bulgarelli-Leva, G., Zvelebil, M., Pirola, L., Vanhaesebroeck, B., Waterfield, M. D., & Panayotou, G. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.4.1722 · Cited by 679 · see citing works
Cyclosporin A, FK-506, and Rapamycin: Pharmacologic Probes of Lymphocyte Signal Transduction
SIGAL, N. H., & Dumont, F. J. (1992) · Annual Review of Immunology · doi:10.1146/annurev.iy.10.040192.002511 · Cited by 674 · see citing works
Stephens, L., Smrcka, A. V., Cooke, F. T., Jackson, T., Sternweis, P. C., & Hawkins, P. T. (1994) · Cell · doi:10.1016/0092-8674(94)90237-2 · Cited by 595 · see citing works
Regulation of eIF-4E BP1 Phosphorylation by mTOR
Hara, K., Yonezawa, K., Kozlowski, M. T., Sugimoto, T., Andrabi, K. I., Weng, Q.-P., Kasuga, M., Nishimoto, I., & Avruch, J. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.42.26457 · Cited by 522 · see citing works
Transduction of interleukin-2 antiapoptotic and proliferative signals via Akt protein kinase
Ahmed, N. N., Grimes, H. L., Bellacosa, A., Chan, T. O., & Tsichlis, P. N. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.8.3627 · Cited by 519 · see citing works
Wortmannin as a unique probe for an intracellular signalling protein, phosphoinositide 3-kinase
Ui, M., Okada, T., Hazeki, K., & Hazeki, O. (1995) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(00)89056-8 · Cited by 519 · see citing works
Calcineurin is required for virulence of Cryptococcus neoformans
Odom, A., Muir, S., Lim, E., Toffaletti, D. L., Perfect, J., & Heitman, J. (1997) · The EMBO Journal · doi:10.1093/emboj/16.10.2576 · Cited by 516 · see citing works
Self-citationRAPT1, a mammalian homolog of yeast Tor, interacts with the FKBP12/rapamycin complex.
Chiu, M. I., Katz, H., & Berlin, V (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.26.12574 · Cited by 481 · see citing works
Scott, P., Brunn, G. J., Kohn, A. D., Roth, R. A., & Lawrence, J. C. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.13.7772 · Cited by 476 · see citing works
Schulte, T. W., Blagosklonny, M. V., Ingui, C., & Neckers, L. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.41.24585 · Cited by 457 · see citing works
Okada, T., Sakuma, L., Fukui, Y., Hazeki, O., & Ui, M. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)41900-4 · Cited by 439 · see citing works
Wortmannin, a microbial product inhibitor of myosin light chain kinase.
Nakanishi, S., Kakita, S., TAKAHASHI, I., Kawahara, K., TSUKUDA, E., Sano, T., Yamada, K., Yoshida, M., Kase, H., & Matsuda, Y. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)45857-7 · Cited by 430 · see citing works
Helliwell, S. B., Wagner, P., Kunz, J., Deuter‐Reinhard, M., Henríquez, R., & Hall, M. N. (1994) · Molecular Biology of the Cell · doi:10.1091/mbc.5.1.105 · Cited by 390 · see citing works
A Signaling Pathway to Translational Control
Brown, E. J., & Schreiber, S. L. (1996) · Cell · doi:10.1016/s0092-8674(00)80125-7 · Cited by 364 · see citing works
Miyazaki, T., Liu, Z., Kawahara, A., Minami, Y., Yamada, K., Tsujimoto, Y., Barsoumian, E. L., Perlmutter, R. M., & Taniguchi, T. (1995) · Cell · doi:10.1016/0092-8674(95)90332-1 · Cited by 362 · see citing works
Cafferkey, R., Young, P. R., McLaughlin, M. M., Bergsma, D. J., Koltin, Y., Sathe, G. M., Faucette, L. F., Eng, W.-K., Johnson, R. K., & Livi, G. P. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.10.6012-6023.1993 · Cited by 309 · see citing works
Zheng, X.-F., Fiorentino, D. F., Chen, J., Crabtree, G. R., & Schreiber, S. L. (1995) · Cell · doi:10.1016/0092-8674(95)90058-6 · Cited by 300 · see citing works
DIFFERENTIAL SIGNALING BY LYMPHOCYTE ANTIGEN RECEPTORS
Alberola‐Ila, J., Takaki, S., Kerner, J. D., & Perlmutter, R. M. (1997) · Annual Review of Immunology · doi:10.1146/annurev.immunol.15.1.125 · Cited by 261 · see citing works
Stack, J. H., & Emr, S. D. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)31729-0 · Cited by 245 · see citing works
TOR Mutations Confer Rapamycin Resistance by Preventing Interaction with FKBP12-Rapamycin
Lorenz, M. C., & Heitman, J. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.46.27531 · Cited by 236 · see citing works
Self-citationvon Manteuffel, S. R., Gingras, A., Ming, X., Sonenberg, N., & Thomas, G. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.9.4076 · Cited by 235 · see citing works
de Groot, R. P., Ballou, L. M., & Sassone‐Corsi, P. (1994) · Cell · doi:10.1016/0092-8674(94)90402-2 · Cited by 232 · see citing works
Rapamycin enhances apoptosis and increases sensitivity to cisplatin in vitro.
Shi, Y., Frankel, A., Radvanyi, L. G., Penn, L. Z., Miller, R. G., & Mills, G. B. (1995) · PubMed · Cited by 225 · see citing works
A Cyclophilin Function in Hsp90-Dependent Signal Transduction
Duina, A. A., Foreman, H.-C. C., Marsh, J. A., Lindquist, S. L., & Gaber, R. F. (1996) · Science · doi:10.1126/science.274.5293.1713 · Cited by 224 · see citing works
Rapamycin Resistance Tied to Defective Regulation of p27 Kip1
Luo, Y., Marx, S. O., Kiyokawa, H., Koff, A., Massagué, J., & Marks, A. R. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.12.6744 · Cited by 210 · see citing works
Calcineurin mediates inhibition by FK506 and cyclosporin of recovery from α-factor arrest in yeast
Poor, F., Parent, S. A., Morin, N. R., Dahl, A., Ramadan, N., Chrebet, G. L., Bostian, K. A., & NIELSEN, J. B. K. (1992) · Nature · doi:10.1038/360682a0 · Cited by 192 · see citing works
Cloning and Characterization of a Wortmannin-sensitive Human Phosphatidylinositol 4-Kinase
Meyers, R. E., & Cantley, L. C. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.7.4384 · Cited by 172 · see citing works
John, A. R. O., Poeta, M. D., Perfect, J. R., & Heitman, J. (1997) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.41.1.156 · Cited by 153 · see citing works
Self-citationInteraction between FKBP12-rapamycin and TOR involves a conserved serine residue.
Stan, R., McLaughlin, M. M., Cafferkey, R., Johnson, R. K., Rosenberg, M. J., & Livi, G. P. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)31592-8 · Cited by 143 · see citing works
Calcineurin is essential in cyclosporin A- and FK506-sensitive yeast strains.
Breuder, T., Hemenway, C. S., Movva, N. R., Cardenas, M. E., & Heitman, J. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.12.5372 · Cited by 135 · see citing works
Self-citationCardenas, M. E., & Heitman, J. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb00277.x · Cited by 116 · see citing works
Self-citationA comparison of demethoxyviridin and wortmannin as inhibitors of phosphatidylinositol 3‐kinase
Woscholski, R., Kodaki, T., McKinnon, M., Waterfield, M. D., & Parker, P. J. (1994) · FEBS Letters · doi:10.1016/0014-5793(94)80482-6 · Cited by 115 · see citing works
Cloning and characterization of a human phosphatidylinositol 4-kinase.
Wong, K., & Cantley, L. C. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)61989-7 · Cited by 98 · see citing works
The Rapamycin and FKBP12 Target (RAFT) Displays Phosphatidylinositol 4-Kinase Activity
Sabatini, D. M., Pierchala, B. A., Barrow, R. K., Schell, M. J., & Snyder, S. H. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.36.20875 · Cited by 82 · see citing works
Ferby, I., Waga, I., Hoshino, M., Kume, K., & Shimizu, T. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.20.11684 · Cited by 79 · see citing works
Cutler, N. S., Heitman, J., & Cardenas, M. E. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.44.27671 · Cited by 78 · see citing works
Self-citationGolgi Localization in Yeast Is Mediated by the Membrane Anchor Region of Rat Liver Sialyltransferase
Schwientek, T., Lorenz, C., & Ernst, J. F. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.10.5483 · Cited by 73 · see citing works
Hemenway, C. S., Dolinski, K. J., Cardenas, M. E., Hiller, M. A., Jones, E. W., & Heitman, J. (1995) · Genetics · doi:10.1093/genetics/141.3.833 · Cited by 62 · see citing works
Self-citationRotonda, J., Burbaum, J. J., Chan, H., Marcy, A. I., & Becker, J. W. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)52995-1 · Cited by 61 · see citing works
Rotonda, J., Burbaum, J. J., Chan, H., et al. (1993) · PubMed · doi:10.2210/pdb1yat/pdb · Cited by 53 · see citing works
Zhu, D., Cardenas, M. E., & Heitman, J. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.42.24831 · Cited by 42 · see citing works
Self-citationMammalian RAFT1 kinase domain provides rapamycin-sensitive TOR function in yeast.Preprint
Alarcón, C. M., Cardenas, M. E., & Heitman, J. (1996) · Genes & Development · doi:10.1101/gad.10.3.279 · Cited by 42 · see citing works
Self-citationCalcineurin mutants render T lymphocytes resistant to cyclosporin A.
Zhu, D., Cardenas, M. E., & Heitman, J. (1996) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)09301-0 · Cited by 35 · see citing works
Self-citationCardenas, M. E., Lorenz, M. C., Hemenway, C. S., & Heitman, J. (1994) · Perspectives in Drug Discovery and Design · doi:10.1007/bf02171739 · Cited by 34 · see citing works
Self-citationCardenas, M. E., Lim, E. Q., & Heitman, J. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.36.20997 · Cited by 34 · see citing works
Self-citationEffects of rapamycin on apoptosis of rheumatoid synovial cells
Migita, K., Eguchi, K., Ichinose, Y., Kawabe, Y., Tsukada, T., Aoyagi, T., & Nagataki, S. (1997) · Clinical & Experimental Immunology · doi:10.1046/j.1365-2249.1997.d01-1002.x · Cited by 25 · see citing works
Yang, M., Wu, W., & Mirocha, C. J. (1996) · Immunopharmacology and Immunotoxicology · doi:10.3109/08923979609052756 · Cited by 8 · see citing works
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Cardenas, M. E., Cutler, N. S., Lorenz, M. C., Como, C. J. D., & Heitman, J. (1999) · Genes & Development · doi:10.1101/gad.13.24.3271 · Cited by 580 · see citing works
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Khalifa, S. A. M., Elias, N., Farag, M. A., Chen, L., Saeed, A., Hegazy, M.-E. F., Moustafa, M. S., Abd El-Wahed, A., Al-Mousawi, S. M., Musharraf, S. G., et al. (2019) · Marine Drugs · doi:10.3390/md17090491 · Cited by 555 · see citing works
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Ruiz‐Villafán, B., Chávez, A., Forero, A. V. F., García-Huante, Y., Romero, A., Sánchez, M., Rocha-Mendoza, D., Sánchez, B., Rodrı́guez-Sanoja, R., Sánchez, S., et al. (2010) · Critical Reviews in Microbiology · doi:10.3109/10408410903489576 · Cited by 384 · see citing works
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Self-citationIntegration of phytochemicals and phytotherapy into cancer precision medicine
Efferth, T., Saeed, M. E. M., Mirghani, E., Alim, A., Yassin, Z., Saeed, E. M., Khalid, H. E., & Daak, S. (2017) · Oncotarget · doi:10.18632/oncotarget.17466 · Cited by 124 · see citing works
Mujoo, K., Haridas, V., Hoffmann, J. J., Wächter, G. A., Hutter, L. K., Lu, Y., Blake, M. E., Jayatilake, G. S., Bailey, D. J., Mills, G. B., et al. (2001) · PubMed · Cited by 122 · see citing works
Yang, X., & van der Donk, W. A. (2013) · Chemistry - A European Journal · doi:10.1002/chem.201300401 · Cited by 120 · see citing works
Wang, P., Cardenas, M. E., Cox, G. M., Perfect, J. R., & Heitman, J. (2001) · EMBO Reports · doi:10.1093/embo-reports/kve109 · Cited by 117 · see citing works
Self-citationActivation of Integrin αVβ3 Regulates Cell Adhesion and Migration to Bone Sialoprotein
Byzova, T. V., Kim, W., Midura, R. J., & Plow, E. F. (2000) · Experimental Cell Research · doi:10.1006/excr.1999.4765 · Cited by 114 · see citing works
Drug resistance in Cryptococcus neoformans
Perfect, J. R., & Cox, G. M. (1999) · Drug Resistance Updates · doi:10.1054/drup.1999.0090 · Cited by 106 · see citing works
Cardenas, M. E., Cruz, M. C., Poeta, M. D., Chung, N., Perfect, J. R., & Heitman, J. (1999) · Clinical Microbiology Reviews · doi:10.1128/cmr.12.4.583 · Cited by 103 · see citing works
Self-citationAnnexin-like alpha giardins: a new cytoskeletal gene family in Giardia lamblia
Weiland, M. E.-L., McArthur, A. G., Morrison, H. G., Sogin, M. L., & Svärd, S. G. (2005) · International Journal for Parasitology · doi:10.1016/j.ijpara.2004.12.009 · Cited by 93 · see citing works
Structures of calcineurin and its complexes with immunophilins–immunosuppressants
Ke, H., & Huai, Q. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(03)01537-7 · Cited by 90 · see citing works
Calpain-calcineurin signaling in the pathogenesis of calcium-dependent disorder.
Wu, H., Tomizawa, K., & Matsui, H. (2007) · PubMed · doi:10.18926/amo/32905 · Cited by 86 · see citing works
Synthesis and evaluation of geldanamycin–testosterone hybrids
Kuduk, S. D., Harris, C. R., Zheng, F. F., Sepp‐Lorenzino, L., Ouerfelli, O., Rosen, N. X., & Danishefsky, S. J. (2000) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/s0960-894x(00)00208-0 · Cited by 82 · see citing works
Production of valuable compounds by molds and yeasts
Demain, A. L., & Martens, E. (2016) · The Journal of Antibiotics · doi:10.1038/ja.2016.121 · Cited by 70 · see citing works
Contractile regulation of the Na+-K+-2Cl−cotransporter in vascular smooth muscle
Akar, F., Jiang, G., Paul, R. J., & O'Neill, W. C. (2001) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.2001.281.2.c579 · Cited by 66 · see citing works
Chen, Y., Guo, H., Du, Z., Liu, X., Che, Y., & Ye, X. (2009) · Cell Proliferation · doi:10.1111/j.1365-2184.2009.00636.x · Cited by 65 · see citing works
Waters, B., Saxena, G., Wanggui, Y., KAU, D. A., Wrigley, S. K., Stokes, R. W., & DAVIES, J. E. (2002) · The Journal of Antibiotics · doi:10.7164/antibiotics.55.407 · Cited by 56 · see citing works
Weisman, R., Finkelstein, S., & Choder, M. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m102090200 · Cited by 52 · see citing works
Hisert, K. B., Kirksey, M., Gomez, J. E., Sousa, A. O., Cox, J. S., Jacobs, W. R., Nathan, C., & McKinney, J. D. (2004) · Infection and Immunity · doi:10.1128/iai.72.9.5315-5321.2004 · Cited by 49 · see citing works
Nilsson, M., Sørensen, O. E., Mörgelin, M., Weineisen, M., Sjöbring, U., & Herwald, H. (2006) · Thrombosis and Haemostasis · doi:10.1160/th05-08-0572 · Cited by 48 · see citing works
New potential targets for antifungal development
Wills, E. A., Redinbo, M. R., Perfect, J. R., & Poeta, M. D. (2000) · Emerging Therapeutic Targets · doi:10.1517/14728222.4.3.265 · Cited by 41 · see citing works
Schneider, G., Oswald, F., Wahl, C., Greten, F. R., Adler, G., & Schmid, R. M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204787200 · Cited by 40 · see citing works
Sánchez, S., & Demain, A. L. (2017) · Springer eBooks · doi:10.1007/978-3-319-51639-4_3 · Cited by 39 · see citing works
Holleran, J. L., Egorin, M. J., Zuhowski, E. G., Parise, R. A., Musser, S. M., & Pan, S. (2003) · Analytical Biochemistry · doi:10.1016/j.ab.2003.08.030 · Cited by 39 · see citing works
Beard, D. J., Hadley, G., Thurley, N., Howells, D., Sutherland, B. A., & Buchan, A. (2018) · International Journal of Stroke · doi:10.1177/1747493018816503 · Cited by 34 · see citing works
Chemical-genetic approaches for exploring the mode of action of natural products
López, A., Parsons, A. B., Nislow, C., Giaever, G. N., & Boone, C. M. (2008) · Birkhäuser Basel eBooks · doi:10.1007/978-3-7643-8595-8_5 · Cited by 38 · see citing works
Calcium Signaling in Excystation of the Early Diverging Eukaryote, Giardia lamblia
Reiner, D. S., Hetsko, M. L., Meszaros, J. G., Sun, C., Morrison, H. G., Brunton, L. L., & Gillin, F. D. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m208033200 · Cited by 36 · see citing works
Crystal structures of cyclophilin and its partners
Ke, H. (2004) · Frontiers in bioscience · doi:10.2741/1396 · Cited by 33 · see citing works
Valuable Secondary Metabolites from Fungi
Demain, A. L. (2014) · Fungal biology · doi:10.1007/978-1-4939-1191-2_1 · Cited by 32 · see citing works
Kim, D. Y., Nam, J., & Rhee, Y. H. (2002) · Biomacromolecules · doi:10.1021/bm010113q · Cited by 32 · see citing works
Bonnet, J.-L., Dusser, M., Bohatier, J., & Laffosse, J. (2003) · Research in Microbiology · doi:10.1016/s0923-2508(03)00085-8 · Cited by 32 · see citing works
Yamada, A., Konishi, K., Cruz, G. L. E., Takehara, M., Morikawa, M., Nakagawa, I., Murakami, M., Abe, T., Todo, S., & Uede, T. (2000) · Transplantation · doi:10.1097/00007890-200003150-00012 · Cited by 32 · see citing works
Isogarcinol Is a New Immunosuppressant
Cen, J., Shi, M., Yang, Y., Fu, Y., Zhou, H., Wang, M., Su, Z., & Wei, Q. (2013) · PLoS ONE · doi:10.1371/journal.pone.0066503 · Cited by 31 · see citing works
Syntheses of photolabile novobiocin analogues
Shen, G., Yu, X. M., & Blagg, B. S. J. (2004) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2004.09.017 · Cited by 28 · see citing works
Tigani, B., Hannon, J. P., Mazzoni, L., & Fozard, J. R. (2001) · European Journal of Pharmacology · doi:10.1016/s0014-2999(01)01515-1 · Cited by 27 · see citing works
Quercetin binds to calcineurin at a similar region to cyclosporin A and tacrolimus
Lei, H., Luo, J., Li, T., Peng, L.-Q., Qi, Y., Jia, Z., & Wei, Q. (2011) · Food Chemistry · doi:10.1016/j.foodchem.2011.01.119 · Cited by 25 · see citing works
Konishi, K., Inobe, M., Yamada, A., Murakami, M., Todo, S., & Uede, T. (2002) · The Journal of Heart and Lung Transplantation · doi:10.1016/s1053-2498(01)00775-6 · Cited by 25 · see citing works
Evidence for a role of nuclear factor-κB in acute hypovolemic hemorrhagic shock
Altavilla, D., Saitta, A., Squadrito, G., Galeano, M., Venuti, S., Guarini, S., Bazzani, C., Bertolini, A., Caputi, A. P., & Squadrito, F. (2002) · Surgery · doi:10.1067/msy.2002.118320 · Cited by 24 · see citing works
Clevenger, R. C., Raibel, J. M., Peck, A. M., & Blagg, B. S. J. (2004) · The Journal of Organic Chemistry · doi:10.1021/jo049848m · Cited by 23 · see citing works
Integration of Phytochemicals and Phytotherapy into Cancer Precision Medicine
Özenver, N., & Efferth, T. (2020) · Human perspectives in health sciences and technology · doi:10.1007/978-3-030-32857-3_16 · Cited by 19 · see citing works
Therapeutic targets in Paracoccidioides brasiliensis: post-transcriptome perspectives.
Amaral, A. C., Fernandes, L., Galdino, A. S., Felipe, M. S. S., Soares, C. M. D. A., & Pereira, M. (2005) · PubMed · Cited by 17 · see citing works
Tomita, M., Suzuki, N., Matsumoto, Y., Hirano, K., UMEDA, N., & Sakai, K. (2000) · Journal of Radiation Research · doi:10.1269/jrr.41.93 · Cited by 17 · see citing works
Holleran, J. L., Fourcade, J., Egorin, M. J., Eiseman, J. L., Parise, R. A., Musser, S. M., White, K. D., Covey, J. M., Forrest, G. L., & Pan, S. (2004) · Drug Metabolism and Disposition · doi:10.1124/dmd.32.5.490 · Cited by 17 · see citing works
Natural Products Mediated Targeting of Virally Infected Cancer
Fatima, I., Kanwal, S., & Mahmood, T. (2019) · Dose-Response · doi:10.1177/1559325818813227 · Cited by 16 · see citing works
Jang, M. J., Jwa, M., Kim, J.-H., & Song, K. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111018200 · Cited by 16 · see citing works
Small Chemicals, Bioactivation, and the Immune System – A Fragile Balance of i‐Tox and Benefits?
Esser, C., & Jux, B. (2009) · Chemistry & Biodiversity · doi:10.1002/cbdv.200900113 · Cited by 15 · see citing works
The importance of Loop 7 for the activity of calcineurin
Liu, P., Huang, C., Wang, H., Zhou, K., Xiao, F., & Wei, Q. (2004) · FEBS Letters · doi:10.1016/j.febslet.2004.09.082 · Cited by 15 · see citing works
Mersmann, J., Tran, N., Latsch, K., Habeck, K., Iskandar, F., Zimmermann, R., & Zacharowski, K. D. (2012) · Resuscitation · doi:10.1016/j.resuscitation.2012.04.001 · Cited by 13 · see citing works
Müller, W. E. G., Steffen, R., Lorenz, B. W. J., Batel, R., Kruse, M., Krasko, A., Müller, I. M., & Schröder, H. C. (2001) · Journal of Experimental Biology · doi:10.1242/jeb.204.13.2197 · Cited by 13 · see citing works
The Hsp90 chaperone complex-A potential target for cancer therapy
Darimont, B. D. (1999) · World Journal of Gastroenterology · doi:10.3748/wjg.v5.i3.195 · Cited by 13 · see citing works
Insulin induces monocytic CXCL8 secretion by the mitogenic signalling pathway
Wurm, S., Neumeier, M., Weigert, J., Wanninger, J., Gerl, M., Gindner, A., Schäffler, A., Aslanidis, C., Schölmerich, J., & Buechler, C. (2008) · Cytokine · doi:10.1016/j.cyto.2008.08.003 · Cited by 12 · see citing works
Ek‐Ramos, M. J., Palma, G. R., & Hernández‐Sotomayor, S. M. T. (2003) · Physiologia Plantarum · doi:10.1034/j.1399-3054.2003.00171.x · Cited by 11 · see citing works
Calderaro, V., Boccellino, M., Cirillo, G., Quagliuolo, L., Cirillo, D., & Giovane, A. (2003) · Journal of the American Society of Nephrology · doi:10.1097/01.asn.0000065632.32856.4c · Cited by 11 · see citing works
Tigani, B., Hannon, J. P., Mazzoni, L., & Fozard, J. R. (2000) · European Journal of Pharmacology · doi:10.1016/s0014-2999(00)00705-6 · Cited by 8 · see citing works
Masoko, P. (2007) · UpSpace Institutional Repository (University of Pretoria) · Cited by 8 · see citing works
Small Molecules as Friends and Foes of the Immune System
Kadow, S., Jux, B., Chmill, S., & Esser, C. (2009) · Future Medicinal Chemistry · doi:10.4155/fmc.09.125 · Cited by 7 · see citing works
Screening of Microbial Extracts for Anticancer Compounds Using Streptomyces Kinase Inhibitor Assay
Shanbhag, P., Bhave, S. V., Vartak, A. P., Kulkarni‐Almeida, A., Mahajan, G., Villanueva, I., & DAVIES, J. E. (2015) · Natural Product Communications · doi:10.1177/1934578x1501000738 · Cited by 7 · see citing works
Anti Cancer Agents from Microbes
Dan, V. M., & Sanawar, R. (2017) · Springer eBooks · doi:10.1007/978-981-10-4284-3_7 · Cited by 7 · see citing works
Drug Resistance in Cryptococcus neoformans
Hanson, K. E., Alexander, B. D., & Perfect, J. R. (2009) · Humana Press eBooks · doi:10.1007/978-1-60327-595-8_20 · Cited by 7 · see citing works
Drug Resistance in Cryptococcosis
Hanson, K. E., Catania, J., Alexander, B. D., & Perfect, J. R. (2017) · Springer eBooks · doi:10.1007/978-3-319-47266-9_20 · Cited by 4 · see citing works
Serine/Threonine Protein Phosphatases in Apoptosis
Gausdal, G., Krakstad, C., Herfindal, L., & Døskeland, S. O. (2007) · Humana Press eBooks · doi:10.1007/978-1-59745-199-4_7 · Cited by 3 · see citing works
Immunsuppressiva zur Verhinderung von Abstoßungsreaktionen nach allogenen Hornhauttransplantationen
Lapp, T., Maier, P. C., Birnbaum, F., Schlunck, G., & Reinhard, T. (2014) · Der Ophthalmologe · doi:10.1007/s00347-013-3016-6 · Cited by 3 · see citing works
Pharmacologically Active Agents of Microbial Origin
Wrigley, S. K. (2014) · ASM Press eBooks · doi:10.1128/9781555817770.ch32 · Cited by 3 · see citing works
Kim, L. (2008) · Cited by 2 · see citing works
Potentials of metabolites of soil fungi
Jadon, K. S., Singh, S. K., & Pathak, R. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-821007-9.00001-2 · Cited by 2 · see citing works
Immunosuppressants: Remarkable Microbial Products
Vaishnav, P., Yoo, Y. J., Yoon, Y. J., & Demain, A. L. (2014) · Wiley eBooks · doi:10.1002/9783527684403.ch4 · Cited by 2 · see citing works
The Aryl Hydrocarbon Receptor (AhR) as a Mediator of Adverse Immune Reactions
Esser, C. (2014) · Wiley eBooks · doi:10.1002/9783527676965.ch6 · Cited by 2 · see citing works
Rapamycin for GVHD prophylaxis - potential for severe myelotoxicity
Davidson, R., Marley, S., & Gordon, M. Y. (2001) · Bone Marrow Transplantation · doi:10.1038/sj.bmt.1702745 · Cited by 2 · see citing works
Microbial pathogens and apoptotic anticancer therapy
Pasechnik, V. (2000) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.9.6.1243 · Cited by 2 · see citing works
Wortmannin as Targeted Therapeutic Agent for the Treatment of Triple-Negative Breast Cancer
Li, J., Liu, F., Liu, Y., Du, J., & Liu, Q. (2016) · Tropical Journal of Pharmaceutical Research · doi:10.4314/tjpr.v15i1.13 · Cited by 1 · see citing works
Marine Derived Pharmaceuticals in Biomedical Research: Current Developments and Future Prospects
Kumar, Y. S., & Swarnalatha, G. V. (2023) · Springer eBooks · doi:10.1007/978-981-99-6770-4_5 · Cited by 1 · see citing works
Clair, J. J. L. (2009) · Royal Society of Chemistry eBooks · doi:10.1039/9781847559890-00044 · Cited by 1 · see citing works
Pandey, A., & Tripathi, S. (2014) · International Research Journal of Pharmacy · doi:10.7897/2230-8407.050206 · Cited by 1 · see citing works
A yeast two-hybrid, systems based approach for the identification of novel pharmaceutical entities
Young, K. H. (1999) · Expert Opinion on Therapeutic Patents · doi:10.1517/13543776.9.7.897 · Cited by 1 · see citing works
Serine/Threonine Kinases and Phosphatases
Girault, J. (2002) · Wiley Encyclopedia of Molecular Medicine · doi:10.1002/0471203076.emm1020 · Cited by 1 · see citing works
Natural products AKTing on signal transduction pathways-molecules and methods
Kiefer, S. (2009) · edoc (University of Basel) · doi:10.5451/unibas-005151603
High‐Throughput Drug Screening Based on Cancer Signaling in Natural Product Screening
Zhang, X., Du, Y., & Yang, J. B. (2014) · Wiley eBooks · doi:10.1002/9783527684403.ch3
Serine/Threonine Kinases and Phosphatases
Girault, J. (2002) · Encyclopedia of Molecular Biology · doi:10.1002/047120918x.emb1408
(2004) · Encyclopedic Dictionary of Genetics, Genomics and Proteomics · doi:10.1002/0471684228.egp10497
- Authors
- Cardenas, M. E., Sanfridson, A., Cutler, N. S., & Heitman, J.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Heitman, Joseph
- Venue
- Trends in Biotechnology
- Publisher
- Elsevier BV
- Published
- 1998-10
- Volume
- 16
- Issue
- 10
- Pages
- 427-433
- ISSN
- 0167-7799 (ISSN-L)
- OpenAlex
- W1968232511
- Cited by
- 101
- References
- 72
- Citations by year
- 2023: 1 · 2020: 2 · 2019: 2 · 2018: 2 · 2017: 4 · 2016: 3 · 2015: 1 · 2014: 7 · 2013: 3 · 2012: 1
- FWCI
- 0.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in biotechnology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ai041937-03, 5k01ca077075-04)
- National Cancer Institute (KO1 CA77075)
- National Institute of Allergy and Infectious Diseases (AI 39115, AI41937)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Health Sciences › Medicine › Pharmacology › Microbial Natural Products and Biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- signaling pathways, natural products, microbial secondary metabolites, cyclosporine, FK506, rapamycin, wortmannin, geldanamycin, immunosuppressants, antiproliferative agents, mechanism of action, target-based drug discovery
- MeSH terms
- Wortmannin, Androstadienes, Animals, Cell Cycle, Enzyme Inhibitors, Fungi, Humans, Immunosuppressive Agents, Quinones, Protein Biosynthesis, Signal Transduction, Benzoquinones, Tacrolimus, Cyclosporine, Apoptosis, HSP90 Heat-Shock Proteins, Calcineurin, Sirolimus, Lactams, Macrocyclic
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