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Chemical Compound Review

Tnp-470     [(3S,4S,5S,6R)-5-methoxy-4- [(2R,3R)-2...

Synonyms: CHEMBL424278, AGM-1470, CHEBI:47708, NSC-642492, DNC001374, ...
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Disease relevance of Tnp-470


High impact information on Tnp-470


Chemical compound and disease context of Tnp-470

  • Fumagillin analogue AGM-1470 potently inhibits angiogenesis with a minimal toxicity in vivo and is expected to be of therapeutic use as a powerful antitumor agent (Ingber et al., Nature, 348:555-557, 1990) [3].
  • The efficacy of combination therapy with cis-diammine-dichloroplatinum (II) (CDDP) and o-(chloroacetyl-carbamoyl) fumagillol (AGM-1470) was evaluated experimentally using a transplantable rat osteosarcoma line, previously established in our laboratory, with a high potential for metastasis [10].

Biological context of Tnp-470


Anatomical context of Tnp-470

  • AGM-1470 acts directly on endothelial cells to inhibit growth factor-induced DNA synthesis, with half maximal and maximal effects obtained at approximately 2 x 10(-10) and 5 x 10(-9) M, respectively [3].
  • Angiogenesis inhibitor TNP-470 (AGM-1470) potently inhibits the tumor growth of hormone-independent human breast and prostate carcinoma cell lines [14].
  • In the present study, we have investigated the effects and the mechanism of action of AGM-1470 on cultured human umbilical vein endothelial cells [3].
  • AGM-1470 was ineffective in significantly inhibiting the proliferation of Ea.hy926 cells, a hybrid cell line obtained by the fusion of human umbilical vein endothelial cells with a human carcinoma cell line, or cEnd.1 cells, a polyoma middle T oncogene-transformed endothelioma cell line derived from mouse embryo [11].
  • When injected subcutaneously or intraperitoneally into mice at pharmacological doses, AGM-1470 induced a significant increase of axillary and mesenteric lymph nodes, respectively [15].

Associations of Tnp-470 with other chemical compounds


Gene context of Tnp-470


Analytical, diagnostic and therapeutic context of Tnp-470

  • We tested the hypothesis that angiogenesis inhibition may affect fertility by studying the reproductive system in either pregnant or nonpregnant cycling mice after treatment with the angiogenesis inhibitor AGM-1470 [6].
  • Using clinical and radiographic criteria, AGM-1470 prevented CIA and significantly suppressed established disease without evidence of immunosuppression [22].
  • AGM-1470, a potent angiogenesis inhibitor, is already engaged in phase I clinical trials because of its effectiveness to restrain tumor growth and its lack of major side effects [15].
  • The s.c. tumours after sacrifice were much smaller in the AGM-1470-treated group (s.c. injection) than in the control groups [23].
  • Furthermore, in the rat blood vessel organ culture assay, AGM-1470 (1-1,000 ng/ml) was found to selectively inhibit the capillary-like tube formation of endothelial cells with a minimal effect on the non-endothelial cell growth [24].


  1. Inhibition of angiogenesis in vivo by interleukin 12. Voest, E.E., Kenyon, B.M., O'Reilly, M.S., Truitt, G., D'Amato, R.J., Folkman, J. J. Natl. Cancer Inst. (1995) [Pubmed]
  2. Inhibition of tumor growth and metastasis of rodent tumors by the angiogenesis inhibitor O-(chloroacetyl-carbamoyl)fumagillol (TNP-470; AGM-1470). Yamaoka, M., Yamamoto, T., Masaki, T., Ikeyama, S., Sudo, K., Fujita, T. Cancer Res. (1993) [Pubmed]
  3. A fumagillin derivative angiogenesis inhibitor, AGM-1470, inhibits activation of cyclin-dependent kinases and phosphorylation of retinoblastoma gene product but not protein tyrosyl phosphorylation or protooncogene expression in vascular endothelial cells. Abe, J., Zhou, W., Takuwa, N., Taguchi, J., Kurokawa, K., Kumada, M., Takuwa, Y. Cancer Res. (1994) [Pubmed]
  4. Docetaxel enhances the therapeutic effect of the angiogenesis inhibitor TNP-470 (AGM-1470) in metastatic human transitional cell carcinoma. Inoue, K., Chikazawa, M., Fukata, S., Yoshikawa, C., Shuin, T. Clin. Cancer Res. (2003) [Pubmed]
  5. The angiogenesis inhibitor tnp-470 effectively inhibits human neuroblastoma xenograft growth, especially in the setting of subclinical disease. Shusterman, S., Grupp, S.A., Barr, R., Carpentieri, D., Zhao, H., Maris, J.M. Clin. Cancer Res. (2001) [Pubmed]
  6. Critical components of the female reproductive pathway are suppressed by the angiogenesis inhibitor AGM-1470. Klauber, N., Rohan, R.M., Flynn, E., D'Amato, R.J. Nat. Med. (1997) [Pubmed]
  7. Simulation of human B-lymphocyte proliferation by AGM-1470, a potent inhibitor of angiogenesis. Antoine, N., Bours, V., Heinen, E., Simar, L.J., Castronovo, V. J. Natl. Cancer Inst. (1995) [Pubmed]
  8. The role of angiogenesis in the tumor growth of Syrian hamster pancreatic cancer cell line HPD-NR. Egawa, S., Tsutsumi, M., Konishi, Y., Kobari, M., Matsuno, S., Nagasaki, K., Futami, H., Yamaguchi, K. Gastroenterology (1995) [Pubmed]
  9. Cell cycle inhibition by the anti-angiogenic agent TNP-470 is mediated by p53 and p21WAF1/CIP1. Zhang, Y., Griffith, E.C., Sage, J., Jacks, T., Liu, J.O. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  10. Efficacy of CDDP and AGM-1470 chemotherapy against lung metastasis in rat osteosarcoma depends on the timing of combined administration. Morishita, T., Mii, Y., Miyauchi, Y., Miura, S., Honoki, K., Aoki, M., Kido, A., Tamai, S., Tsutsumi, M., Konishi, Y. Jpn. J. Clin. Oncol. (1997) [Pubmed]
  11. AGM-1470, a potent angiogenesis inhibitor, prevents the entry of normal but not transformed endothelial cells into the G1 phase of the cell cycle. Antoine, N., Greimers, R., De Roanne, C., Kusaka, M., Heinen, E., Simar, L.J., Castronovo, V. Cancer Res. (1994) [Pubmed]
  12. Disposition and metabolism of the angiogenic moderator O-(chloroacetyl-carbamoyl) fumagillol (TNP-470; AGM-1470) in human hepatocytes and tissue microsomes. Placidi, L., Cretton-Scott, E., de Sousa, G., Rahmani, R., Placidi, M., Sommadossi, J.P. Cancer Res. (1995) [Pubmed]
  13. The influence of angiogenesis inhibitor AGM-1470 on immune system status and tumor growth in vitro. Schoof, D.D., Obando, J.A., Cusack, J.C., Goedegebuure, P.S., Brem, H., Eberlein, T.J. Int. J. Cancer (1993) [Pubmed]
  14. Angiogenesis inhibitor TNP-470 (AGM-1470) potently inhibits the tumor growth of hormone-independent human breast and prostate carcinoma cell lines. Yamaoka, M., Yamamoto, T., Ikeyama, S., Sudo, K., Fujita, T. Cancer Res. (1993) [Pubmed]
  15. In vitro and in vivo stimulation of the murine immune system by AGM-1470, a potent angiogenesis inhibitor. Antoine, N., Daukandt, M., Heinen, E., Simar, L.J., Castronovo, V. Am. J. Pathol. (1996) [Pubmed]
  16. Antiangiogenic chemotherapeutic agents: characterization in comparison to their tumor growth inhibition in human renal cell carcinoma models. Schirner, M., Hoffmann, J., Menrad, A., Schneider, M.R. Clin. Cancer Res. (1998) [Pubmed]
  17. Methionine aminopeptidase (type 2) is the common target for angiogenesis inhibitors AGM-1470 and ovalicin. Griffith, E.C., Su, Z., Turk, B.E., Chen, S., Chang, Y.H., Wu, Z., Biemann, K., Liu, J.O. Chem. Biol. (1997) [Pubmed]
  18. Suppression of collagen-induced arthritis by an angiogenesis inhibitor, AGM-1470, in combination with cyclosporin: reduction of vascular endothelial growth factor (VEGF). Oliver, S.J., Cheng, T.P., Banquerigo, M.L., Brahn, E. Cell. Immunol. (1995) [Pubmed]
  19. The potent angioinhibin AGM-1470 stimulates normal but not human tumoral lymphocytes. Antoine, N., Daukandt, M., Locigno, R., Heinen, E., Simar, L.J., Castronovo, V. Tumori. (1996) [Pubmed]
  20. Suppression of arthritis and protection from bone destruction by treatment with TNP-470/AGM-1470 in a transgenic mouse model of rheumatoid arthritis. de Bandt, M., Grossin, M., Weber, A.J., Chopin, M., Elbim, C., Pla, M., Gougerot-Pocidalo, M.A., Gaudry, M. Arthritis Rheum. (2000) [Pubmed]
  21. Selective inhibition of protein kinase C, mitogen-activated protein kinase, and neutrophil activation in response to calcium pyrophosphate dihydrate crystals, formyl-methionyl-leucyl-phenylalanine, and phorbol ester by O-(chloroacetyl-carbamoyl) fumagillol (AGM-1470; TNP-470). Tudan, C., Jackson, J.K., Pelech, S.L., Attardo, G., Burt, H. Biochem. Pharmacol. (1999) [Pubmed]
  22. Angiogenesis inhibition suppresses collagen arthritis. Peacock, D.J., Banquerigo, M.L., Brahn, E. J. Exp. Med. (1992) [Pubmed]
  23. Increased growth and incidence of lymph node metastases due to the angiogenesis inhibitor AGM-1470. Hori, K., Li, H.C., Saito, S., Sato, Y. Br. J. Cancer (1997) [Pubmed]
  24. Potent anti-angiogenic action of AGM-1470: comparison to the fumagillin parent. Kusaka, M., Sudo, K., Fujita, T., Marui, S., Itoh, F., Ingber, D., Folkman, J. Biochem. Biophys. Res. Commun. (1991) [Pubmed]
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