Alvespimycin TFA  (Synonyms: 17-DMAG TFA; KOS-1022 TFA; NSC 707545 TFA)

Alvespimycin (17-DMAG) TFA is a potent inhibitor of Hsp90, binding to Hsp90 with an EC₅₀ of 62 nM^[1].

Alvespimycin (17-DMAG) TFA inhibits the growth of the human cancer cell lines SKBR3 and SKOV3, which overexpress Hsp90 client protein Her2, and causes down-regulation of Her2 as well as induction of Hsp70 consistent with Hsp90 inhibition, for Her2 degradation with EC₅₀ of 8 nM and 46 nM in SKBR3 and SKOV3 cells, respectively; for Hsp70 induction with EC₅₀ of 4 nM and 14 nM in SKBR3 and SKOV3 cells, respectively^[1].
Compared with the vehicle control, Alvespimycin (17-DMAG) TFA dose-dependent apoptosis (P<0.001 averaged across 24- and 48-hour time points) at concentrations of 50 nM to 500 nM, which represent pharmacologically attainable doses. Similar to many other agents, Alvespimycin (17-DMAG) TFA also demonstrates time-dependent apoptosis (P <0.001, averaged across all doses) in chronic lymphocytic leukemia (CLL) cells with extended exposure from 24 to 48 hours. In addition,Alvespimycin (17-DMAG) TFA is much more potent after 24 and 48 hours of treatment than 17-AAG^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

The tumors are grown for two months before the start of i.p. injections every four days over one month with 0, 50, 100 and 200 mg/kg dipalmitoyl-radicicol or 0, 5, 10 and 20 mg/kg Alvespimycin (17-DMAG) TFA. Despite sample heterogeneity, the HSP90 inhibitor-treated animals have significantly lower tumour volumes than the vehicle control-treated animals^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

730.77

C₃₄H₄₉F₃N₄O₁₀

Solid

Pale purple to purple

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Room temperature in continental US; may vary elsewhere.

-20°C, sealed storage, away from moisture and light

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)

• [1]. Ge J, et al. Design, synthesis, and biological evaluation of hydroquinone derivatives of 17-amino-17-demethoxygeldanamycin as potent, water-soluble inhibitors of Hsp90. J Med Chem. 2006 Jul 27;49(15):4606-15.  [Content Brief]

  [2]. Hertlein E, et al. 17-DMAG targets the nuclear factor-kappaB family of proteins to induce apoptosis in chronic lymphocytic leukemia: clinical implications of HSP90 inhibition. Blood. 2010 Jul 8;116(1):45-53.  [Content Brief]

  [3]. Henke A, et al. Reduced Contractility and Motility of Prostatic Cancer-Associated Fibroblasts after Inhibition of Heat Shock Protein 90. Cancers (Basel). 2016 Aug 24;8(9). pii: E77.  [Content Brief]