17-AAG from Geldanamycin.com, Biochemicals for Cancer Research

17-(allylamino)-17-demethoxygeldanamycins

17-AAG is a water soluble, ansamycin antibiotic which binds to Hsp90 (Heat Shock Protein 90) and alters its function. Hsp90 plays a key role in regulating the physiology of cells exposed to environmental stress and in maintaining the 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. 17-AAG 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. The current research interest for 17-AAG lies in its ability to inhibit the growth of malignant tumors. Another focus is its ability to sensitize cancer cells to some other anti-cancer chemotherapeutic compounds. 17-AAG also represents a less toxic analog of the anti-tumor compound geldanamycin.

Product No:A-1256
Chemical Formula: C₃₁H₄₂N₂O₉
M.W.: 574.86
CAS No: [75747-14-7]
RTECS: LX8920000
Handling: Toxic, Hygroscopic
Storage: +4°C

Literature References

1. Neckers L, Ivy SP. Heat shock protein 90. Curr Opin Oncol. 2003 Nov;15(6):419-24.

2. Solit DB, Scher HI, Rosen N. Hsp90 as a therapeutic target in prostate cancer. Semin Oncol. 2003 Oct;30(5):709-16.

3. Fumo G, Akin C, Metcalfe DD, Neckers L. 17-Allylamino-17-demethoxygeldanamycin (17-AAG) is effective in down-regulating mutated, constitutively activated KIT protein in human mast cells. Blood. 2004 Feb 1;103(3):1078-84. Epub 2003 Oct 09.

4. Jia W, Yu C, Rahmani M, Krystal G, Sausville EA, Dent P, Grant S. Synergistic antileukemic interactions between 17-AAG and UCN-01 involve interruption of RAF/MEK- and AKT-related pathways. Blood. 2003 Sep 1;102(5):1824-32. Epub 2003 May 08.

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

6. Yang J, Yang JM, Iannone M, Shih WJ, Lin Y, Hait WN., Disruption of the EF-2 kinase/Hsp90 protein complex: a possible mechanism to inhibit glioblastoma by geldanamycin. Cancer Res. 2001. May 15;61(10):4010-6.

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

8. Munster PN, Marchion DC, Basso AD, Rosen N., Degradation of HER2 by ansamycins induces growth arrest and apoptosis in cells with HER2 overexpression via a HER3, phosphatidylinositol 3'-kinase-AKT-dependent pathway. Cancer Res. 2002. Jun 1;62(11):3132-7.

9. Munster PN, Srethapakdi M, Moasser MM, Rosen N., Inhibition of heat shock protein 90 function by ansamycins causes the morphological and functional differentiation of breast cancer cells. Cancer Res. 2001. Apr 1;61(7):2945-52.

17-AAG A-1256

17-(allylamino)-17-demethoxygeldanamycins

Literature References