geldanamycin   Click here for help

GtoPdb Ligand ID: 9829

PDB Ligand
Compound class: Natural product
Comment: Geldanamycin is naturally occurring benzoquinone antibacterial and Hsp90 inhibitor [6]. It was originally isolated from Streptomyces hygroscopicus var. geldanus [5]. Total chemical syntheses have been reported [1,4,7]. Geldanamycin has been demonstrated to promote the proteasomal degradation of oncogenic signaling proteins, so synthetic/semisynthetic derivatives are of interest as potential oncology therapeutics [3].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 11
Hydrogen bond donors 3
Rotatable bonds 5
Topological polar surface area 163.48
Molecular weight 560.27
XLogP 1.02
No. Lipinski's rules broken 1

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES COC1CC(C)CC2=C(OC)C(=O)C=C(C2=O)NC(=O)C(=CC=CC(C(C(=CC(C1O)C)C)OC(=O)N)OC)C
Isomeric SMILES CO[C@H]1C[C@H](C)CC2=C(OC)C(=O)C=C(C2=O)NC(=O)/C(=C/C=C\[C@@H]([C@H](/C(=C/[C@@H]([C@H]1O)C)/C)OC(=O)N)OC)/C
InChI 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
InChI Key QTQAWLPCGQOSGP-KSRBKZBZSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Andrus MB, Meredith EL, Simmons BL, Soma Sekhar BB, Hicken EJ. (2002)
Total synthesis of (+)-geldanamycin and (-)-o-quinogeldanamycin with use of asymmetric anti- and syn-glycolate aldol reactions.
Org Lett, 4 (20): 3549-52. [PMID:12323066]
2. Gavenonis J, Jonas NE, Kritzer JA. (2014)
Potential C-terminal-domain inhibitors of heat shock protein 90 derived from a C-terminal peptide helix.
Bioorg Med Chem, 22 (15): 3989-93. [PMID:24984936]
3. Kitson RRA, Kitsonová D, Siegel D, Ross D, Moody CJ. (2024)
Geldanamycin, a Naturally Occurring Inhibitor of Hsp90 and a Lead Compound for Medicinal Chemistry.
J Med Chem, 67 (20): 17946-17963. [PMID:39361055]
4. Qin HL, Panek JS. (2008)
Total synthesis of the Hsp90 inhibitor geldanamycin.
Org Lett, 10 (12): 2477-9. [PMID:18489177]
5. Sasaki K, Rinehart Jr KL, Slomp G, Grostic MF, Olson EC. (1970)
Geldanamycin. I. Structure assignment.
J Am Chem Soc, 92 (26): 7591-3. [PMID:5490719]
6. Whitesell L, Mimnaugh EG, De Costa B, Myers CE, Neckers LM. (1994)
Inhibition of heat shock protein HSP90-pp60v-src heteroprotein complex formation by benzoquinone ansamycins: essential role for stress proteins in oncogenic transformation.
Proc Natl Acad Sci U S A, 91 (18): 8324-8. [PMID:8078881]
7. Zhang Z, Li Y, Zhang R, Yu X. (2021)
Total Synthesis of Geldanamycin.
J Org Chem, 86 (21): 15063-15075. [PMID:34657428]