Geldanamycinfeatured
WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#:205922
CAS#:30562-34-6
Description: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.
Price and Availability
Geldanamycin, purity > 98%, is in stock. The same say shipping after order is received.
Chemical Structure
Theoretical Analysis
MedKoo Cat#: 205922Name: GeldanamycinCAS#: 30562-34-6Chemical Formula: C29H40N2O9Exact Mass: 560.27338Molecular Weight: 560.6359Elemental 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.
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
InChi Key:QTQAWLPCGQOSGP-KSRBKZBZSA-N
InChi Code:InChI=1S/C29H40N2O9/c1-15-11-19-25(34)20(14-21(32)27(19)39-7)31-28(35)16(2)9-8-10-22(37-5)26(40-29(30)36)18(4)13-17(3)24(33)23(12-15)38-6/h8-10,13-15,17,22-24,26,33H,11-12H2,1-7H3,(H2,30,36)(H,31,35)/b10-8-,16-9+,18-13+/t15-,17+,22+,23+,24-,26+/m1/s1
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=CC=C(C)C(NC(C1=O)=CC2=O)=O)=O
Technical Data
Additional Information
Geldanamycin was originally discovered in the organism Streptomyces hygroscopicus. It is a macrocyclic polyketide that is synthesized by a Type I polyketide synthase. The genes gelA, gelB, and gelC encode for the polyketide synthase. The PKS is first loaded with 3-amino-5-hydroxybenzoic acid (AHBA). It then utilizes malonyl-CoA, methylmalonyl-CoA, and methoxymalonyl-CoA to synthesize the precursor molecule Progeldanamycin. This precursor is subjected to several enzymatic and non-enzymatic tailoring steps to produce the active molecule Geldanamycin, which include hydroxylation, o-methylation, carbamoylation, and oxidation.
References
1: Gorska M, Popowska U, Sielicka-Dudzin A, Kuban-JankowskaA, Sawczuk W, Knap N, Cicero G, Wozniak F. Geldanamycin and itsderivatives 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-canceractivities. 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, andchimeric inhibitors of the Hsp90 N-terminal ATP binding site. Curr TopMed 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 InvestigDrugs. 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 novelcancer chemotherapeutic agents. Curr Pharm Des. 2005;11(9):1131-8.Review. PubMed PMID: 15853661.
7: Sausville EA. Geldanamycin analogs. J Chemother. 2004 Nov;16 Suppl4:68-9. Review. PubMed PMID: 15688614.
8: Liao ZY, Zhen YS. [Advances in antitumor activity of the hsp90inhibitor 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 ofgeldanamycin 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 aclass of antitumor drugs targeting the heat shock protein 90 family ofmolecular chaperones. Cell Stress Chaperones. 2001 Apr;6(2):105-12.Review. Erratum in: Cell Stress Chaperones 2001 Jul;6(3):295. PubMedPMID: 11599571; PubMed Central PMCID: PMC434387.
