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Chemical Compound Review

DMAG     [ (3S,5S,6R,7S,8E,10R,11S,12Z,14 E)-21-(2...

Synonyms: alvespimycin, AC1NRBWB, CHEMBL383824, KOS-1022, SureCN5449716, ...
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Disease relevance of KOS

  • The present results are from preclinical toxicity studies evaluating 17-DMAG in rats and dogs [1].

High impact information on KOS


Biological context of KOS


Anatomical context of KOS


Associations of KOS with other chemical compounds

  • An accurate, sensitive, robust and selective liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for the determination of 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin hydrochloride (17-DMAG) in human plasma has been developed and validated [6].

Gene context of KOS

  • Crystal structure and molecular modeling of 17-DMAG in complex with human Hsp90 [7].
  • Therefore, we have investigated the effects of the orally bioavailable Hsp90 inhibitor 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG) on the radiosensitivity of human tumor cells in vitro and grown as tumor xenografts [4].
  • We describe the 1.75 A resolution crystal structure of human Hsp90 alpha (residues 9-236) complexed with 17-desmethoxy-17-N,N-dimethylaminoethylamino-geldanamycin (17-DMAG) [7].
  • For mechanistic insight, the G(2)- and S-phase checkpoints were evaluated in 17-DMAG-treated cells [4].
  • EXPERIMENTAL DESIGN: The activity of 17-DMAG, in vivo, was evaluated for inhibition of fibroblast growth factor (FGF)-2-induced angiogenesis in s.c. implanted Matrigel in mice [3].

Analytical, diagnostic and therapeutic context of KOS

  • Finally, the effect of in vivo administration of 17-DMAG in combination with radiation on the growth rate of xenograft tumors was determined [4].
  • RESULTS: Daily oral administration of 17-DMAG affected the angiogenic response in Matrigel in a dose-dependent manner [3].
  • Development and validation of a liquid chromatography/tandem mass spectrometry method for the determination of the novel anticancer agent 17-DMAG in human plasma [6].
  • Tissue and plasma 17-DMAG concentrations were measured by HPLC/MS at selected time-points on days 1 and 5 [1].
  • By immunohistochemistry, 17-DMAG significantly reduced vessel area and numbers of proliferating tumor cells in sections [8].


  1. Preclinical toxicity of a geldanamycin analog, 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG), in rats and dogs: potential clinical relevance. Glaze, E.R., Lambert, A.L., Smith, A.C., Page, J.G., Johnson, W.D., McCormick, D.L., Brown, A.P., Levine, B.S., Covey, J.M., Egorin, M.J., Eiseman, J.L., Holleran, J.L., Sausville, E.A., Tomaszewski, J.E. Cancer Chemother. Pharmacol. (2005) [Pubmed]
  2. ZAP-70 is a novel conditional heat shock protein 90 (Hsp90) client: inhibition of Hsp90 leads to ZAP-70 degradation, apoptosis, and impaired signaling in chronic lymphocytic leukemia. Castro, J.E., Prada, C.E., Loria, O., Kamal, A., Chen, L., Burrows, F.J., Kipps, T.J. Blood (2005) [Pubmed]
  3. Antiangiogenic properties of 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin: an orally bioavailable heat shock protein 90 modulator. Kaur, G., Belotti, D., Burger, A.M., Fisher-Nielson, K., Borsotti, P., Riccardi, E., Thillainathan, J., Hollingshead, M., Sausville, E.A., Giavazzi, R. Clin. Cancer Res. (2004) [Pubmed]
  4. Enhanced tumor cell radiosensitivity and abrogation of G2 and S phase arrest by the Hsp90 inhibitor 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin. Bull, E.E., Dote, H., Brady, K.J., Burgan, W.E., Carter, D.J., Cerra, M.A., Oswald, K.A., Hollingshead, M.G., Camphausen, K., Tofilon, P.J. Clin. Cancer Res. (2004) [Pubmed]
  5. Determination of the heat shock protein 90 inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin in plasma by liquid chromatography-electrospray mass spectrometry. Hwang, K., Scripture, C.D., Gutierrez, M., Kummar, S., Figg, W.D., Sparreboom, A. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. (2006) [Pubmed]
  6. Development and validation of a liquid chromatography/tandem mass spectrometry method for the determination of the novel anticancer agent 17-DMAG in human plasma. Moreno-Farre, J., Asad, Y., Pacey, S., Workman, P., Raynaud, F.I. Rapid Commun. Mass Spectrom. (2006) [Pubmed]
  7. Crystal structure and molecular modeling of 17-DMAG in complex with human Hsp90. Jez, J.M., Chen, J.C., Rastelli, G., Stroud, R.M., Santi, D.V. Chem. Biol. (2003) [Pubmed]
  8. Inhibition of heat shock protein 90 impairs epidermal growth factor-mediated signaling in gastric cancer cells and reduces tumor growth and vascularization in vivo. Lang, S.A., Klein, D., Moser, C., Gaumann, A., Glockzin, G., Dahlke, M.H., Dietmaier, W., Bolder, U., Schlitt, H.J., Geissler, E.K., Stoeltzing, O. Mol. Cancer Ther. (2007) [Pubmed]
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