Geldanamycin
Geldanamycin is a benzoquinone ansamycin antibiotic that binds to Hsp90 (Heat Shock Protein 90) and inhibits its function. HSP90 client proteins play important roles in the regulation of the cell cycle, cell growth, cell survival, apoptosis, angiogenesis and oncogenesis. Hsp90-geldanamycin complex. PDB 1yet Geldanamycin induces the degradation of proteins that are mutated in tumor cells such as v-Src, Bcr-Abl and p53 preferentially over their normal cellular counterparts. This effect is mediated via HSP90. Despite its potent antitumor potential, geldanamycin presents several major drawbacks as a drug candidate (namely, hepatotoxicity) that have led to the development of geldanamycin analogues.
1: Gorska M, Popowska U, Sielicka-Dudzin A, Kuban-Jankowska A, Sawczuk W, Knap N, Cicero G, Wozniak F. Geldanamycin and its derivatives as Hsp90 inhibitors. Front Biosci. 2012 Jun 1;17:2269-77. Review. PubMed PMID: 22652777.
2: Fukuyo Y, Hunt CR, Horikoshi N. Geldanamycin and its anti-cancer activities. Cancer Lett. 2010 Apr 1;290(1):24-35. Epub 2009 Oct 21. Review. PubMed PMID: 19850405.
3: Hadden MK, Lubbers DJ, Blagg BS. Geldanamycin, radicicol, and chimeric inhibitors of the Hsp90 N-terminal ATP binding site. Curr Top Med Chem. 2006;6(11):1173-82. Review. PubMed PMID: 16842154.
4: Chiosis G, Caldas Lopes E, Solit D. Heat shock protein-90 inhibitors: a chronicle from geldanamycin to today's agents. Curr Opin Investig Drugs. 2006 Jun;7(6):534-41. Review. PubMed PMID: 16784024.
5: Neckers L. Chaperoning oncogenes: Hsp90 as a target of geldanamycin. Handb Exp Pharmacol. 2006;(172):259-77. Review. PubMed PMID: 16610363.
6: Miyata Y. Hsp90 inhibitor geldanamycin and its derivatives as novel cancer chemotherapeutic agents. Curr Pharm Des. 2005;11(9):1131-8. Review. PubMed PMID: 15853661.
7: Sausville EA. Geldanamycin analogs. J Chemother. 2004 Nov;16 Suppl 4:68-9. Review. PubMed PMID: 15688614.
8: Liao ZY, Zhen YS. [Advances in antitumor activity of the hsp90 inhibitor geldanamycin]. Yao Xue Xue Bao. 2001 Sep;36(9):716-20. Review. Chinese. PubMed PMID: 12580116.
9: Blagosklonny MV. Hsp-90-associated oncoproteins: multiple targets of geldanamycin and its analogs. Leukemia. 2002 Apr;16(4):455-62. Review. PubMed PMID: 11960322.
10: Ochel HJ, Eichhorn K, Gademann G. 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. Review. Erratum in: Cell Stress Chaperones 2001 Jul;6(3):295. PubMed PMID: 11599571; PubMed Central PMCID: PMC434387.
2: Fukuyo Y, Hunt CR, Horikoshi N. Geldanamycin and its anti-cancer activities. Cancer Lett. 2010 Apr 1;290(1):24-35. Epub 2009 Oct 21. Review. PubMed PMID: 19850405.
3: Hadden MK, Lubbers DJ, Blagg BS. Geldanamycin, radicicol, and chimeric inhibitors of the Hsp90 N-terminal ATP binding site. Curr Top Med Chem. 2006;6(11):1173-82. Review. PubMed PMID: 16842154.
4: Chiosis G, Caldas Lopes E, Solit D. Heat shock protein-90 inhibitors: a chronicle from geldanamycin to today's agents. Curr Opin Investig Drugs. 2006 Jun;7(6):534-41. Review. PubMed PMID: 16784024.
5: Neckers L. Chaperoning oncogenes: Hsp90 as a target of geldanamycin. Handb Exp Pharmacol. 2006;(172):259-77. Review. PubMed PMID: 16610363.
6: Miyata Y. Hsp90 inhibitor geldanamycin and its derivatives as novel cancer chemotherapeutic agents. Curr Pharm Des. 2005;11(9):1131-8. Review. PubMed PMID: 15853661.
7: Sausville EA. Geldanamycin analogs. J Chemother. 2004 Nov;16 Suppl 4:68-9. Review. PubMed PMID: 15688614.
8: Liao ZY, Zhen YS. [Advances in antitumor activity of the hsp90 inhibitor geldanamycin]. Yao Xue Xue Bao. 2001 Sep;36(9):716-20. Review. Chinese. PubMed PMID: 12580116.
9: Blagosklonny MV. Hsp-90-associated oncoproteins: multiple targets of geldanamycin and its analogs. Leukemia. 2002 Apr;16(4):455-62. Review. PubMed PMID: 11960322.
10: Ochel HJ, Eichhorn K, Gademann G. 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. Review. Erratum in: Cell Stress Chaperones 2001 Jul;6(3):295. PubMed PMID: 11599571; PubMed Central PMCID: PMC434387.
| Chemical | |
|---|---|
| CAS Num | 30562-34-6 |
| Chemical Formula | C29H40N2O9 |
| Molecular Weight | 560.6359 |
| IUPAC Chemical Name | (4E,6Z,8S,9S,10E,12S,13R,14S,16R)-13-hydroxy-8,14,19-trimethoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl carbamate |
| Exact Mass | 560.27338 |
| Elemental Analysis | C, 62.13; H, 7.19; N, 5.00; O, 25.68 |
| Synonym | NSC 122750; NSC-122750; NSC122750; U 29135; U-29135; U29135. Geldanamycin. |
| Solubility | Soluble in DMSO, not in water |
| SMILES Code | NC(O[C@@H](/C(C)=C/[C@H](C)[C@@H](O)[C@@H](OC)C[C@H](C)CC1=C2OC)[C@@H](OC)/C=C\C=C(C)\C(NC(C1=O)=CC2=O)=O)=O |
| Biological | |
| Targets and Effects | Hsp90 (Heat Shock Protein 90) inhibitor |
| Pathways | Apoptosis |
| Physical | |
| Appearance | Solid powder |
| Purity | >98% (or refer to the Certificate of Analysis) |
| Shipping Condition | Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs. |
| Storage Condition | Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years). |
| Shelf Life | >5 years if stored properly |
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