| Name | KW-2478 |
| Description | KW-2478 is a non-ansamycin HSP90 inhibitor with IC50 of 3.8 nM. |
| Cell Research | To measure the IC50, OPM-2/green fluorescent protein (GFP) cells, KMS-11 cells, OPM-2/GFP and other cells are plated into 96-well plates and treat with KW-2478. After 72 hours of cultivation, cell viability is determined using Cell Proliferation Reagent WST-1. WST reagent is added to the wells, followed by incubation for 4 hours at 37 °C. After that, the absorbance at 450 nm with reference at 650 nm is measured with a microplate spectrophotometer. To examine time dependency of antiproliferative activity of KW-2478, the cells are plated into 96-well V-bottomed plates and treated with KW-2478. After 0 hour and at intervals from 3 to 72 hours at 37 °C, the supernatant is aspirated. After drug-free medium is added to the wells, the supernatant is aspirated again. Finally, drug-free medium is added to the wells, and the plates are further incubated for the remainder of the 72-hour period, followed by measurement of cell viabil(Only for Reference) |
| Kinase Assay | Hsp90 Binding Assay: Human Hsp90α solution (0.5 μg/mL) is fixed on 96-well plates, followed by blocking with TBS containing 1% bovine serum albumin. KW-2478 solutions is added to the wells, and bRD is added to a concentration of 0.1 μmol/L. After removal of solution, poly-HRP streptavidin solution dilutes with poly-HRP dilution buffer is added to the wells. After removal of solution, equal volumes of TMB peroxidase substrate and peroxidase solution B are added to the wells. To stop the HRP reaction, 2 mol/L H2SO4 are added, followed by measurement of absorbance at 450 nm using a microplate spectrophotometer. |
| In vitro | KW-2478 inhibits the binding of bRD to Hsp90α with IC50 of 3.8 nM. KW-2478 degradates the Hsp90 client proteins, including FGFR3 and IGF-1Rβand c-Raf-1. KW-2478 reduces the level of phosphorylated Erk1/2. KW-2478 induces apoptosis by cleavage of PARP, a substrate of caspase-3 In U266 cells,. KW-2478 has Time dependency of antiproliferative activity, consecutive drug exposure for at least 12 hours is necessary to to exert potent antitumor activity. KW-2478 downregulates the translocation products of IgH locus. KW-2478 inhibits the transcription of c-Maf and cyclin D1 genes by mainly suppressing the function of Cdk9. [1] KW-2478 has potent and broad growth inhibitory activities against various cell lines, KW-2478 inhibites cancer cell growth in all cell lines, with EC50 of 101-252 nM, 81.4-91.4 nM and 120-622 nM for B-cell lymphoma, mantle cell lymphoma and multiple myeloma, respectively. KW-2478 also shows potent growth inhibitory activity in primary CLL and NHL cells with EC50 of 40-170 nM and 200-400 nM, respectively. [2]. |
| In vivo | KW-2478 suppresses tumor growth and induces the degradation of client proteins in tumors in NCI-H929 s.c. inoculated model at doses of 100 mg/kg or more. KW-2478 reduces both serum M protein and MM tumor burden in the bone marrow in OPM-2/GFP i.v. inoculated mouse model at doses of 100 mg/kg. [1] |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| Solubility Information | DMSO : 106 mg/mL (184.5 mM)
Ethanol : 3 mg/mL (5.22 mM)
H2O : < 1 mg/mL (insoluble or slightly soluble)
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| Keywords | inhibit | Heat shock proteins | KW-2478 | KW 2478 | Inhibitor | HSP |
| Inhibitors Related | Ethoxyquin | SNX0723 | Tamoxifen | DN401 | SNX2112 | Ganetespib | Teprenone | Elesclomol | Rifabutin | Palmitic acid | Paeoniflorin | Tamoxifen Citrate |
| Related Compound Libraries | Apoptosis Compound Library | Bioactive Compound Library | Hematonosis Compound Library | Anti-Cancer Clinical Compound Library | Drug Repurposing Compound Library | Inhibitor Library | NO PAINS Compound Library | Bioactive Compounds Library Max | Anti-Cancer Active Compound Library | Anti-Cancer Drug Library |
United States
