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    InvivoChem Cat #: V0889
    CAS #: 819812-04-9Purity ≥98%

    Description: KW-2478 (KW 2478; KW2478) is a nonansamycin inhibitor of HSP90 (Heat Shock Protein 90) with potential antitumor activity. It inhibits HSP90 with an IC50 of 3.8 nM. It demonstrates significant in vivo antitumor efficacy in NCI-H929 tumor-bearing SCID mice.

    References: Clin Cancer Res. 2010 May 15;16(10):2792-802.

    Related CAS #: 819812-04-9 (free base); 819812-18-5 (HCl);

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    Molecular Weight (MW)574.66
    CAS No.819812-04-9
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 115 mg/mL (200.1 mM)
    Water: <1 mg/mL
    Ethanol: 3 mg/mL (5.2 mM)
    Solubility (In vivo)30% propylene glycol, 5% Tween 80, 65% D5W: 10mg/mL  

    Synonym: KW-2478; KW2478; KW 2478.

    Chemical Name: 2-(2-ethyl-3,5-dihydroxy-6-(3-methoxy-4-(2-morpholinoethoxy)benzoyl)phenyl)-N,N-bis(2-methoxyethyl)acetamide


    InChi Code: InChI=1S/C30H42N2O9/c1-5-22-23(19-28(35)32(11-13-37-2)12-14-38-3)29(25(34)20-24(22)33)30(36)21-6-7-26(27(18-21)39-4)41-17-10-31-8-15-40-16-9-31/h6-7,18,20,33-34H,5,8-17,19H2,1-4H3


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    In Vitro

    In vitro activity: 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. 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

    Kinase 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.

    Cell Assay:  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 viability.

    In VivoKW-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.
    Animal modelNCI-H929 tumors s.c. inoculated in SCID mice, OPM-2/GFP i.v. inoculated mouse model
    Formulation & DosageDissolved in 0.9% sodium chloride solution; 25, 50 , 100 and 200 mg/kg; oral gavage

    Clin Cancer Res. 2010 May 15;16(10):2792-802.

    These protocols are for reference only. InvivoChem does not independently validate these methods.


    Chemical structure and Hsp90 binding activity of KW-2478. Clin Cancer Res. 2010 May 15;16(10):2792-802. 


    Effects of KW-2478 on FGFR3, c-Maf, and cyclin D1 proteins. Clin Cancer Res. 2010 May 15;16(10):2792-802. 


    Time dependency of antiproliferative activity of KW-2478. Clin Cancer Res. 2010 May 15;16(10):2792-802. 


    Time dependent effects of KW-2478 on the IgH translocation products. Clin Cancer Res. 2010 May 15;16(10):2792-802. 


    Effects of KW-2478 in NCI-H929 tumors s.c. inoculated in SCID mice. Clin Cancer Res. 2010 May 15;16(10):2792-802. 


    In vivo antitumor activity of KW-2478 in MM orthotopic model. Clin Cancer Res.2010 May 15;16(10):2792-802. 


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