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Chemical Compound Review

NSC-622141     (2E,4E)-N-[2-hydroxy-2- [(1E,3E,5E)-6-[(2...

Synonyms: AC1NTS03, NSC622141, HMS1362M13, IDI1_002201, 52665-74-4, ...
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Disease relevance of NSC622141


High impact information on NSC622141

  • Moreover, manumycin, a specific inhibitor of FTase, was effective in inhibiting mitosis and growth in these cells [6].
  • Using synchronized BY-2 cells, manumycin completely blocked mitosis when added at the early S phase but not when added at the G2 phase [6].
  • We show here that two farnesyltransferase inhibitors, manumycin and gliotoxin, suppress the Multivulva phenotype resulting from an activated let-60 ras mutation, but not the Multivulva phenotype resulting from mutations in the lin-1 gene or the lin-15 gene, which act downstream and upstream of let-60 ras, respectively, in the signaling pathway [7].
  • Similarly, treatment of cells with a Ras farnesyltransferase inhibitor, manumycin A, strongly inhibited the HA-dependent MMP-2 secretion [8].
  • Similarly, a Ras farnesyltransferase inhibitor, manumycin A, and a MEK1 inhibitor, U0126, suppressed MMP secretion in a dose-dependent manner, whereas a PI3 kinase inhibitor, wortmannin, could not [9].

Chemical compound and disease context of NSC622141


Biological context of NSC622141

  • Manumycin plus paclitaxel has enhanced cytotoxic effects and increased apoptotic cell death in ATC cells in vitro compared with either drug by itself [1].
  • EBS contribution to hormone induction was prevented by manumycin A, an inhibitor of Ras farnesylation [14].
  • Raf-1 phosphorylation at Ser338 by BK was inhibited by manumycin A and GW 5074 [15].
  • Furthermore, cells expressing wild-type IKKbeta and IKKbeta mutated in the activation loop at Cys-179 exhibited covalent homotypic dimerization of IKKbeta in response to manumycin A, whereas substitution of Cys-662 and -716 conferred protection against dimer formation [2].
  • However, the mechanism of the manumycin-induced apoptosis is not fully understood [16].

Anatomical context of NSC622141


Associations of NSC622141 with other chemical compounds


Gene context of NSC622141


Analytical, diagnostic and therapeutic context of NSC622141


  1. Manumycin enhances the cytotoxic effect of paclitaxel on anaplastic thyroid carcinoma cells. Yeung, S.C., Xu, G., Pan, J., Christgen, M., Bamiagis, A. Cancer Res. (2000) [Pubmed]
  2. Binding of manumycin A inhibits IkappaB kinase beta activity. Bernier, M., Kwon, Y.K., Pandey, S.K., Zhu, T.N., Zhao, R.J., Maciuk, A., He, H.J., Decabo, R., Kole, S. J. Biol. Chem. (2006) [Pubmed]
  3. Lysophosphatidic acid signals through mitogen-activated protein kinase-extracellular signal regulated kinase in ovarian theca cells expressing the LPA1/edg2-receptor: involvement of a nonclassical pathway? Budnik, L.T., Brunswig-Spickenheier, B., Mukhopadhyay, A.K. Mol. Endocrinol. (2003) [Pubmed]
  4. Enhancement of manumycin A-induced apoptosis by methoxyamine in myeloid leukemia cells. She, M., Pan, I., Sun, L., Yeung, S.C. Leukemia (2005) [Pubmed]
  5. Apoptosis of medulloblastoma cells in vitro follows inhibition of farnesylation using manumycin A. Wang, W., Macaulay, R.J. Int. J. Cancer (1999) [Pubmed]
  6. Protein farnesyltransferase in plants: molecular characterization and involvement in cell cycle control. Qian, D., Zhou, D., Ju, R., Cramer, C.L., Yang, Z. Plant Cell (1996) [Pubmed]
  7. Ras farnesyltransferase inhibitors suppress the phenotype resulting from an activated ras mutation in Caenorhabditis elegans. Hara, M., Han, M. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  8. Hyaluronan-CD44s signaling regulates matrix metalloproteinase-2 secretion in a human lung carcinoma cell line QG90. Zhang, Y., Thant, A.A., Machida, K., Ichigotani, Y., Naito, Y., Hiraiwa, Y., Senga, T., Sohara, Y., Matsuda, S., Hamaguchi, M. Cancer Res. (2002) [Pubmed]
  9. The Ras-mitogen-activated protein kinase pathway is critical for the activation of matrix metalloproteinase secretion and the invasiveness in v-crk-transformed 3Y1. Liu, E., Thant, A.A., Kikkawa, F., Kurata, H., Tanaka, S., Nawa, A., Mizutani, S., Matsuda, S., Hanafusa, H., Hamaguchi, M. Cancer Res. (2000) [Pubmed]
  10. Raf-1 kinase activation by angiotensin II in adrenal glomerulosa cells: roles of Gi, phosphatidylinositol 3-kinase, and Ca2+ influx. Smith, R.D., Baukal, A.J., Dent, P., Catt, K.J. Endocrinology (1999) [Pubmed]
  11. Manumycin and gliotoxin derivative KT7595 block Ras farnesylation and cell growth but do not disturb lamin farnesylation and localization in human tumour cells. Nagase, T., Kawata, S., Tamura, S., Matsuda, Y., Inui, Y., Yamasaki, E., Ishiguro, H., Ito, T., Miyagawa, J., Mitsui, H., Yamamoto, K., Kinoshita, M., Matsuzawa, Y. Br. J. Cancer (1997) [Pubmed]
  12. Nisamycin, a new manumycin group antibiotic from Streptomyces sp. K106. I. Taxonomy, fermentation, isolation, physico-chemical and biological properties. Hayashi, K., Nakagawa, M., Nakayama, M. J. Antibiot. (1994) [Pubmed]
  13. The structure of manumycin. III. Absolute configuration and conformational studies. Thiericke, R., Stellwaag, M., Zeeck, A., Snatzke, G. J. Antibiot. (1987) [Pubmed]
  14. Regulation of rat cytochrome P450C24 (CYP24) gene expression. Evidence for functional cooperation of Ras-activated Ets transcription factors with the vitamin D receptor in 1,25-dihydroxyvitamin D(3)-mediated induction. Dwivedi, P.P., Omdahl, J.L., Kola, I., Hume, D.A., May, B.K. J. Biol. Chem. (2000) [Pubmed]
  15. Bradykinin B2 receptor mediates NF-kappaB activation and cyclooxygenase-2 expression via the Ras/Raf-1/ERK pathway in human airway epithelial cells. Chen, B.C., Yu, C.C., Lei, H.C., Chang, M.S., Hsu, M.J., Huang, C.L., Chen, M.C., Sheu, J.R., Chen, T.F., Chen, T.L., Inoue, H., Lin, C.H. J. Immunol. (2004) [Pubmed]
  16. Bcl-2-associated X protein is the main mediator of manumycin a-induced apoptosis in anaplastic thyroid cancer cells. Pan, J., Huang, H., Sun, L., Fang, B., Yeung, S.C. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  17. Angiogenesis inhibition in the in vivo antineoplastic effect of manumycin and paclitaxel against anaplastic thyroid carcinoma. Xu, G., Pan, J., Martin, C., Yeung, S.C. J. Clin. Endocrinol. Metab. (2001) [Pubmed]
  18. Inhibition of corneal inflammation by the topical use of Ras farnesyltransferase inhibitors: selective inhibition of macrophage localization. Sonoda, K., Sakamoto, T., Yoshikawa, H., Ashizuka, S., Ohshima, Y., Kishihara, K., Nomoto, K., Ishibashi, T., Inomata, H. Invest. Ophthalmol. Vis. Sci. (1998) [Pubmed]
  19. v-Src requires Ras signaling for the suppression of gap junctional intercellular communication. Ito, S., Ito, Y., Senga, T., Hattori, S., Matsuo, S., Hamaguchi, M. Oncogene (2006) [Pubmed]
  20. YC-1-induced cyclooxygenase-2 expression is mediated by cGMP-dependent activations of Ras, phosphoinositide-3-OH-kinase, Akt, and nuclear factor-kappaB in human pulmonary epithelial cells. Chang, M.S., Lee, W.S., Chen, B.C., Sheu, J.R., Lin, C.H. Mol. Pharmacol. (2004) [Pubmed]
  21. Cytochrome c release is upstream to activation of caspase-9, caspase-8, and caspase-3 in the enhanced apoptosis of anaplastic thyroid cancer cells induced by manumycin and paclitaxel. Pan, J., Xu, G., Yeung, S.C. J. Clin. Endocrinol. Metab. (2001) [Pubmed]
  22. p44/42 mitogen-activated protein kinase is involved in the expression of ornithine decarboxylase in leukaemia L1210 cells. Flamigni, F., Facchini, A., Capanni, C., Stefanelli, C., Tantini, B., Caldarera, C.M. Biochem. J. (1999) [Pubmed]
  23. Effects of the farnesyltransferase inhibitor UCF-1C/manumycin on growth and p21-ras post-translational processing in NIH3T3 cells. Servais, P., Gulbis, B., Fokan, D., Galand, P. Int. J. Cancer (1998) [Pubmed]
  24. Manumycin inhibits ras signal transduction pathway and induces apoptosis in COLO320-DM human colon tumour cells. Di Paolo, A., Danesi, R., Nardini, D., Bocci, G., Innocenti, F., Fogli, S., Barachini, S., Marchetti, A., Bevilacqua, G., Del Tacca, M. Br. J. Cancer (2000) [Pubmed]
  25. Manumycin inhibits farnesyltransferase and induces apoptosis of drug-resistant interleukin 6-producing myeloma cells. Frassanito, M.A., Cusmai, A., Piccoli, C., Dammacco, F. Br. J. Haematol. (2002) [Pubmed]
  26. Suppression of human pancreatic cancer growth in BALB/c nude mice by manumycin, a farnesyl:protein transferase inhibitor. Ito, T., Kawata, S., Tamura, S., Igura, T., Nagase, T., Miyagawa, J.I., Yamazaki, E., Ishiguro, H., Matasuzawa, Y. Jpn. J. Cancer Res. (1996) [Pubmed]
  27. Increased expression of heat shock protein 70 in adherent ovarian cancer and mesothelioma following treatment with manumycin, a farnesyl transferase inhibitor. Hu, W., Wu, W., Yeung, S.C., Freedman, R.S., Kavanagh, J.J., Verschraegen, C.F. Anticancer Res. (2002) [Pubmed]
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