Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C31H43N3O8 |
Molecular Weight | 585.6884 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 6 / 6 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CO[C@H]1C[C@H](C)CC2=C(NCC=C)C(=O)C=C(NC(=O)\C(C)=C\C=C[C@H](OC)[C@@H](OC(N)=O)\C(C)=C\[C@H](C)[C@H]1O)C2=O
InChI
InChIKey=AYUNIORJHRXIBJ-TXHRRWQRSA-N
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
Tanespimycin (17-allylamino-17-demethoxygeldanamycin,
17-AAG) is a synthetic analogue of geldanamycin, an antibiotic
first purified in 1970 from Streptomyces hygroscopicus. Tanespimycin is an Hsp90 inhibitor that has demonstrated the potential to disrupt the activity of multiple oncogenes and cell signaling pathways implicated in tumor growth, including HER2, a key pathway in breast cancer. Tanespimycin was being under development by Kosan Biosciences. It was in phase 3 clinical development with bortezomib for the treatment of multiple myeloma (MM). However, in 2010 the company halted development of tanespimycin, during late-stage clinical trials as a potential treatment for multiple myeloma. While no definitive explanation was given, it has been suggested that Bristol-Myers Squibb halted development over concerns of the financial feasibility of tanespimycin development given the 2014 expiry of the patent on this compound, and the relative expense of manufacture.
CNS Activity
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24344631
Curator's Comment: Studies on the tissue distribution of Tanespimycin (17-AAG) in mice showed that it penetrates the blood brain barrier.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2095165 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14508491 |
5.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT00546780
Solution, IV, 340mg/m2, twice weekly for 2 weeks (3 week cycle), 60 minutes infusion
Route of Administration:
Intravenous
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16061882
Tanespimycin (17-AAG) significantly inhibits cell proliferation
in both synovial sarcoma cell
lines Fuji and SYO-1 in a dose- and
time-dependent manner. The 17-AAG IC50 values for
synovial sarcoma monolayer models treated for 72 hours were
both 0.038 uM/L. HER2 and FGFR3 were reduced to extremely
low levels by 5 uM/L 17-AAG.
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FDA ORPHAN DRUG |
469915
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NCI_THESAURUS |
C2516
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FDA ORPHAN DRUG |
191304
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EU-Orphan Drug |
EU/3/04/256
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FDA ORPHAN DRUG |
191504
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C37899
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64153
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SUB33510
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TANESPIMYCIN
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330507
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DB05134
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SS-61
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C112765
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4GY0AVT3L4
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CHEMBL109480
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6505803
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75747-14-7
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8815
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