tanespimycin   Click here for help

GtoPdb Ligand ID: 7751

Synonyms: 17-AAG | 17-allylamino-17-demethoxygeldanamycin | 17-N-allylamino-17-demethoxygeldanamycin | 17AAG | compound 4 [PMID:15978816]
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: 17-AAG inhibits the activity of hsp90. The compound is a derivative of the antibacterial geldanamycin.
As with other natural products, there is some ambiguity in the absolute stereochemistry annotated by different online resources. PubChem records an alternative isomer with a Z bond at position 12 which has CID 6505803. 17-AAG acts as a femtomolar inhibitor of Met tyrosine kinase receptor-dependent urokinase-plasminogen activation [5].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 11
Hydrogen bond donors 4
Rotatable bonds 7
Topological polar surface area 166.28
Molecular weight 585.31
XLogP 1.8
No. Lipinski's rules broken 1
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Isomeric SMILES C=CCNC1=C2C[C@@H](C)C[C@H](OC)[C@H](O)[C@@H](C)/C=C(\C)/[C@@H]([C@H](/C=C/C=C(/C(=O)NC(=CC1=O)C2=O)\C)OC)OC(=O)N
InChI InChI=1S/C31H43N3O8/c1-8-12-33-26-21-13-17(2)14-25(41-7)27(36)19(4)15-20(5)29(42-31(32)39)24(40-6)11-9-10-18(3)30(38)34-22(28(21)37)16-23(26)35/h8-11,15-17,19,24-25,27,29,33,36H,1,12-14H2,2-7H3,(H2,32,39)(H,34,38)/b11-9+,18-10+,20-15+/t17-,19+,24+,25+,27-,29+/m1/s1
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Summary of Clinical Use Click here for help
The EMA has granted orphan drug designation for this compound as a treatment for malignant gastrointestinal stromal tumours (GIST), chronic myeloid leukemia (CML, and the FDA for the same indication) and multiple myeloma (MM). 17-AAG was investigated as a potential antineoplastic therapy [2]. Click here to link to ClinicalTrials.gov's list of registered tanespimycin trials. There are no currently active trials (Sept 2014).
Mechanism Of Action and Pharmacodynamic Effects Click here for help
17-AAG binds to the common N-terminal domain ATP/ATP binding site on both α and β Hsp90 isoforms. This destabilises Hsp90 client proteins, a number of which are oncogenic, and cells undergo apoptosis [1].