Geldanamycin from Geldanamycin.com, Biochemicals for Cancer Research

Streptomyces hygroscopicus

Geldanamycin is a benzoquinone ansamycin antibiotic which binds to Hsp90 (Heat Shock Protein 90) and alters its function. Hsp90 is a highly conserved and very abundant protein in the cytosol of both eukaryotic and prokaryotic cells. Hsp90 plays a key role in regulating the physiology of cells exposed to environmental stress and in maintaining malignant phenotype of tumor cells.

Hsp90 client proteins play important roles in the regulation of the cell cycle, cell growth, cell survival, apoptosis and oncogenesis. Geldanamycin binds with a high affinity into the ATP binding pocket in Hsp90 and induces the degradation of proteins that require this chaperone for conformational maturation.

Product No: G-1047
Chemical Formula: C₂₉H₄0N₂O₉
M.W.: 560.6
CAS No: [30562-34-6]
RTECS: LX8920000
Storage: 20°C, Toxic

Literature References

1. Geldanamycin and herbimycin A induce apoptotic killing of B chronic lymphocytic leukemia cells and augment the cells' sensitivity to cytotoxic drugs. Jones DT, Addison E, North JM, Lowdell MW, Hoffbrand AV, Mehta AB, Ganeshaguru K, Folarin NI, Wickremasinghe RG. Blood. 2004 Mar 1;103(5):1855-61. Epub 2003 Oct 23.

2. Geldanamycin, a Ligand of Heat Shock Protein 90, Inhibits the Replication of Herpes Simplex Virus Type 1 In Vitro. Li YH, Tao PZ, Liu YZ, Jiang JD. Antimicrob Agents Chemother. 2004 Mar;48(3):867-872.

3. Geldanamycin, an inhibitor of Hsp90, sensitizes human tumour cells to radiation. Machida H, Matsumoto Y, Shirai M, Kubota N. Int J Radiat Biol. 2003 Dec;79(12):973-80.

4. Natural product origins of Hsp90 inhibitors. Uehara Y. Curr Cancer Drug Targets. 2003 Oct;3(5):325-30.

5. Regulation of 17-AAG-induced apoptosis: role of Bcl-2, Bcl-xL, and Bax downstream of 17-AAG-mediated downregulation of Akt, Raf-1 and Src kinases. Nimmanapalli R, O'Bryan E, Kuhn D, Yamaguchi H, Wang HG, Bhalla KN. Blood. 2003 Jul 1;102(1):269-75. Epub 2003 Mar 06.

6. Geldanamycin inhibits the production of inflammatory cytokines in activated macrophages by reducing the stability and translation of cytokine transcripts. Wax S, Piecyk M, Maritim B, Anderson P. Arthritis Rheum 2003 Feb;48(2):541-50

7 Involvement of heat-shock protein 90 in the interleukin-6-mediated signaling pathway through STAT3. Sato N, Yamamoto T, Sekine Y, Yumioka T, Junicho A, Fuse H, Matsuda T. Biochem Biophys Res Commun 2003 Jan 24;300(4):847-52

8. Geldanamycin decreases Raf-1 and Akt levels and induces apoptosis in neuroblastomas. Kim S, Kang J, Hu W, Evers BM, Chung DH. Int J Cancer 2003 Jan 20;103(3):352-9.

9. Hsp-90-associated oncoproteins: multiple targets of geldanamycin and its analogs. Blagosklonny MV. Leukemia 2002 Apr;16(4):455-62.

10. HSP90 as a new therapeutic target for cancer therapy: the story unfolds. Maloney A, Workman P. Expert Opin Biol Ther 2002 Jan;2(1):3-24.

11. Geldanamycin: the prototype of a class of antitumor drugs targeting the heat shock protein 90 family of molecular chaperones. Cell Stress Chaperones 2001 Apr;6(2):105-12.

12. Geldanamycin and its analogue 17-allylamino-17-demethoxygeldanamycin lowers Bcr-Abl levels and induces apoptosis and differentiation of Bcr-Abl-positive human leukemic blasts.Nimmanapalli R, O'Bryan E, Bhalla K. Cancer Res 2001 Mar 1;61(5):1799-804.

13. Geldanamycin, an inhibitor of heat shock protein 90 (Hsp90) mediated Cancer Research has anti-inflammatory effects and interacts with glucocorticoid receptor in vivo. Br J Pharmacol 2000 Sep;131(1):13-6.

14. Geldanamycin as a potential anti-cancer agent: its molecular target and biochemical activity. Neckers L, Schulte TW, Mimnaugh E. Invest New Drugs 1999;17(4):361-73

15. Signal-transduction cascades as targets for therapeutic intervention by natural products. Cardenas ME, Sanfridson A, Cutler NS, Heitman J. Trends Biotechnol 1998 Oct;16(10):427-33

16. The benzoquinone ansamycin 17-allylamino-17-demethoxygeldanamycin binds to HSP90 and shares important biologic activities with geldanamycin. Schulte TW, Neckers LM. Cancer Chemother Pharmacol 1998;42(4):273-9

17. Potent inhibition of inducible nitric oxide synthase by geldanamycin, a tyrosine kinase inhibitor, in endothelial, smooth muscle cells, and in rat aorta. Joly GA, Ayres M, Kilbourn RG. FEBS Lett 1997 Feb 10;403(1):40-4

18. Growth inhibition of virus transformed cells in vitro and antitumor activity in vivo of geldanamycin and its derivatives. Sasaki K, Yasuda H, Onodera K. J Antibiot (Tokyo) 1979 Aug;32(8):849-51

19. Effects of geldanamycin and its derivatives on RNA-directed DNA polymerase and infectivity of Rauscher leukemia virus. Li LH, Clark TD, Cowie CH, Rinehart KL Jr. Cancer Treat Rep 1977 Aug;61(5):815-24

Geldanamycin G-1047

Streptomyces hygroscopicus

Literature References