Back قلدانامیسین AZB Geldanamycin German گلدانامیسین Persian Geldanamysiini Finnish Geldanamycine French Geldanamicina Italian Geldanamycyna Polish Geldanamicin Serbo-Croatian Geldanamicin Serbian

Geldanamycin

Geldanamycin
Names
IUPAC 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
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
DrugBank
UNII
  • 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 checkY
    Key: QTQAWLPCGQOSGP-KSRBKZBZSA-N checkY
  • 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
    Key: QTQAWLPCGQOSGP-KSRBKZBZBP
  • Key: QTQAWLPCGQOSGP-KSRBKZBZSA-N
  • NC(=O)O[C@H]1C(/C)=C/[C@H](C)[C@@H](O)[C@@H](OC)C[C@H](C)C\C2=C(/OC)C(=O)\C=C(\NC(=O)C(\C)=C\C=C/[C@@H]1OC)C2=O
Properties
C29H40N2O9
Molar mass 560.64 g/mol
Appearance Gold-yellow fine crystalline powder
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY verify (what is checkY☒N ?)

Geldanamycin is a 1,4-benzoquinone ansamycin antitumor antibiotic that inhibits the function of Hsp90 (Heat Shock Protein 90) by binding to the unusual ADP/ATP-binding pocket of the protein.[1] HSP90 client proteins play important roles in the regulation of the cell cycle, cell growth, cell survival, apoptosis, angiogenesis and oncogenesis.[2]

Hsp90-geldanamycin complex. PDB 1yet[3]

Geldanamycin induces the degradation of proteins that are mutated or overexpressed in tumor cells such as v-Src, Bcr-Abl, p53, and ERBB2. This effect is mediated via HSP90. Despite its potent antitumor potential, geldanamycin presents several major drawbacks as a drug candidate such as hepatotoxicity, further, Jilani et al.. reported that geldanamycin induces the apoptosis of erythrocytes under physiological concentrations.[4] These side effects have led to the development of geldanamycin analogues, in particular analogues containing a derivatisation at the 17 position:

  1. ^ Schulte, T. W.; Akinaga, S.; Soga, S.; Sullivan, W.; Stensgard, B.; Toft, D.; Neckers, L. M. (1998). "Antibiotic radicicol binds to the N-terminal domain of Hsp90 and shares important biologic activities with geldanamycin". Cell Stress & Chaperones. 3 (2): 100–108. doi:10.1379/1466-1268(1998)003<0100:ARBTTN>2.3.CO;2 (inactive 1 November 2024). PMC 312953. PMID 9672245.{{cite journal}}: CS1 maint: DOI inactive as of November 2024 (link)
  2. ^ Wayne, N.; Mishra, P.; Bolon, D.N. (2011). "Hsp90 and Client Protein Maturation". Molecular Chaperones. Methods Mol Biol. Vol. 787. pp. 33–44. doi:10.1007/978-1-61779-295-3_3. ISBN 978-1-61779-294-6. PMC 5078872. PMID 21898225.
  3. ^ Stebbins, C. E.; Russo, A. A.; Schneider, C.; Rosen, N.; Hartl, F. U.; Pavletich, N. P. (1997). "Crystal structure of an Hsp90-geldanamycin complex: Targeting of a protein chaperone by an antitumor agent". Cell. 89 (2): 239–250. doi:10.1016/S0092-8674(00)80203-2. PMID 9108479. S2CID 5253110.
  4. ^ Jilani, Kashif; Qadri, Syed M.; Lang, Florian (2013). "Geldanamycin-Induced Phosphatidylserine Translocation in the Erythrocyte Membrane". Cell Physiol Biochem. 32 (6): 1600–1609. doi:10.1159/000356596. PMID 24335345.
From Wikipedia, the free encyclopedia · View on Wikipedia

Developed by Nelliwinne