| Name | Tanespimycin |
| Description | Tanespimycin (KOS 953) is an Hsp90 inhibitor (IC50=5 nM) and is selective. Tanespimycin depletes intracellular STK38/NDR1 and decreases STK38 kinase activity. Tanespimycin also downregulated stk38 gene expression. |
| Cell Research | Cells were seeded in 96-well plates at 2,000 cells per well in a final culture volume of 100 μl for 24 h before the addition of increasing concentrations of 17-AAG that was incubated for 5 days. Viable cell number was determined using the Celltiter 96 AQueous Nonradioactive Cell Proliferation Assay. The value of the background absorbance at 490 nm (A490) of wells not containing cells was subtracted. Percentage of viable cells ? (A490 of 17-AAG treated sample/A490 untreated cells) × 100. The IC50 was defined as the concentration that gave rise to 50% viable cell number [1]. |
| Kinase Assay | Purified native Hsp90 protein or cell lysates in lysis buffer (20 mM HEPES, pH 7.3, 1 mM EDTA, 5 mM MgCl2, 100 mM KCl) were incubated with or without 17-AAG for 30 min at 4 °C, and then incubated with biotin-GM linked to streptavidin magnetic beads for 1 h at 4 °C. Tubes were placed on a magnetic rack, and the unbound supernatant removed. The magnetic beads were washed three times in lysis buffer and heated for 5 min at 95 °C in SDS–PAGE sample buffer. Samples were analyzed on SDS protein gels, and western blots done using indicated antibodies. Bands in the western blots were quantified, and the percentage inhibition of binding of Hsp90 to the biotin-GM was calculated. The IC50 reported is the concentration of 17-AAG needed to cause half-maximal inhibition of binding. For in vitro reconstitution, 5 μM of purified Hsp90 was combined with 1 μM each of Hsp70, Hsp40, p23, and Hop purified proteins [1]. |
| Animal Research | B10.BR mice were inoculated with 5×10^5 lymphoma cells through intraperitoneal injection. Seven days following tumor implantation, the mice were I.P. injected with 17-AAG or vehicle (10% DMSO + 40% Cremophor EL: Ethanol (3:1) (v/v) + 50 % PBS) every other day for three weeks. At the cessation of treatment, mice were monitored up to 80 days post tumor cell injection. To determine the effects of 17-AAG on lymphoma initiation in vivo, secondary B10.BR recipient mice were implanted by intraperitoneal injection of 1×10^5 lymphoma cells from the spleens of first-round mice that had been treated with 17-AAG or vehicle. These mice were followed up to 160 days post tumor cell injection to monitor differences in tumor initiation between the mice [4]. |
| In vitro | METHODS: Human A-431, A549, BGC-823, HepG2, HUVEC, L02, and MDA-MB-231 cells were treated with Tanespimycin (0-10 μM) for 72 hours, and the cell growth inhibition was detected by MTT assay.
RESULTS: Tanespimycin inhibited A-431 (IC50=89 nM), A549 (IC50=81 nM), BGC-823 (IC50=847 nM), HepG2 (IC50=91 nM), HUVEC (IC50=282 nM), and L02 (IC50=99) nM), MDA-MB-231 (IC50=0.28 μM) cell growth. [1]
METHODS: CCA cells were treated with Tanespimycin (0.6 μM) for 72 hours, and the expression levels of target proteins were detected by Western Blot.
RESULTS: Tanespimycin downregulated Bcl-2, Survivin and Cyclin B1 and upregulated cleaved PARP. [2] |
| In vivo | METHODS: To study the antitumor activity of Tanespimycin, lymphoma-inoculated mice were intraperitoneally injected with Tanespimycin (5-40 mg/kg) every other day for three weeks.
RESULTS: Tanespimycin inhibited lymphoma in vivo. [3] |
| Storage | keep away from direct sunlight,keep away from moisture,store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature. |
| Solubility Information | 10% DMSO+40% PEG300+5% Tween 80+45% Saline : 1 mg/mL (1.71 mM), Sonication is recommended.
DMSO : 50.5 mg/mL (86.22 mM), Sonication is recommended.
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| Keywords | tumor | Tanespimycin | stk38 | prostate | NSC-330507 | NSC330507 | Mitophagy | Mitochondrial Autophagy | KOS-953 | KOS953 | Inhibitor | inhibit | HSP90 | HSP | HER2 | Heat shock proteins | CP-127374 | CP127374 | cancer | Bacterial | Autophagy | Apoptosis | Antibiotic | A549 |
| Inhibitors Related | Neomycin sulfate | Stavudine | Cysteamine hydrochloride | Kanamycin sulfate | Sulfamethoxazole sodium | Terbinafine hydrochloride | Hydroxychloroquine | Doxycycline | Tributyrin | Paeonol | Dimethyl sulfoxide | Alginic acid |
| Related Compound Libraries | Highly Selective Inhibitor Library | Failed Clinical Trials Compound Library | Bioactive Compound Library | Kinase Inhibitor Library | Anti-Cancer Clinical Compound Library | Drug Repurposing Compound Library | Microbial Natural Product Library | Natural Product Library for HTS | Anti-Aging Compound Library | Bioactive Compounds Library Max | Anti-Cancer Active Compound Library |
United States
