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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
Structure of TANESPIMYCIN

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

HIDE SMILES / InChI

Molecular Formula C31H43N3O8
Molecular Weight 585.6884
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 6 / 6
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

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

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
5.0 nM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown
Primary
Unknown
Primary
Unknown

Cmax

ValueDoseCo-administeredAnalytePopulation
8532.2 ng/mL
340 mg/m² single, intravenous
TANESPIMYCIN plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
20768 ng × h/mL
340 mg/m² single, intravenous
TANESPIMYCIN plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
3.4 h
340 mg/m² single, intravenous
TANESPIMYCIN plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
10%
TANESPIMYCIN plasma
Homo sapiens

PubMed

Sample Use Guides

In Vivo Use Guide
Solution, IV, 340mg/m2, twice weekly for 2 weeks (3 week cycle), 60 minutes infusion
Route of Administration: Intravenous
In Vitro Use Guide
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.
Substance Class Chemical
Record UNII
4GY0AVT3L4
Record Status Validated (UNII)
Record Version