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SNX-2112 is a potent synthetic heat shock protein 90 inhibitor with an IC50 of 0.92 μM for K562 cells. The heat shock protein 90 (Hsp90) chaperone not only regulates the conformational maturation but also stables the structures of oncogenic kinases as well as transcription factors. SNX-2112 is an active metabolite of the compounds SNX-5542. SNX-2112 is rapidly transformed form SNX-5542 after administration. In a panel of tumor cell lines, SNX-2112 degraded HER2 and mutant epidermal growth factor receptor and inhibited extracellular signal-modulated kinase and Akt activation.SNX-2112 inducen a Rb-dependent G1 arrest with subsequent apoptosis. which accumulates in tumors relative to normal tissues.
| Cell Experiment | |
|---|---|
| Cell lines | BT474, SKBR-3, SKOV-3, MDA-468, MCF-7 and H1650 cancer cells |
| Preparation method | Determining cell viability by seeding 2-5 × 103 cells per well in 96- well plates and treating with SNX-2112 24 hours after plating in complete medium (200 μL). Testing each drug concentration in eight wells. After a 96-h incubation ,using the Alamar blue viability test to assay cells . Flow cytometry is done using nuclei stained with ethidium bromide and isolated via the Nusse protocol |
| Concentrations | 0-500 nM |
| Incubation time | 24 hours |
| Animal Experiment | |
|---|---|
| Animal models | 5 ?106 MM.1S cells are inoculated subcutaneously in the Fox Chase SCID mice (6-7 weeks old). |
| Formulation | SNX-5422 is dissolved in 1% carboxy methylcellulose/0.5% Tween 80 at 10 mg/mL and stored at 4 癈 for in vivo stud |
| Dosages | 20 or 40 mg/kg |
| Administration | SNX-5422 is administered orally 3 times per week, total 3 weeks. |
| Molecular Weight | 464.48 |
| Formula | C23H27F3N4O3 |
| CAS Number | 908112-43-6 |
| Solubility (25°C) | DMSO 83 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
[4] Natsuko Fukuoka, et al. SNX-2112 Induces Apoptosis and Autophagy of Nara-H Cells
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| Hsp70-derived octapeptide
Hsp70-derived octapeptide is a conserved octapeptide of the C-terminal end of Hsp70, which physically interacts with tetratricopeptide repeat (TPR) motifs. |
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