Name | 2-[2-ethyl-3,5-dihydroxy-6-[3-methoxy-4-(2-morpholin-4-ylethoxy)benzoyl]phenyl]-N,N-bis(2-methoxyethyl)acetamide |
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Synonyms |
cc-326
pound not KW2478 pound not KW 2478 QC-7253 UNII-QY50S617NM 2-(2-Ethyl-3,5-dihydroxy-6-{3-methoxy-4-[2-(4-morpholinyl)ethoxy]benzoyl}phenyl)-N,N-bis(2-methoxyethyl)acetamide Benzeneacetamide, 2-ethyl-3,5-dihydroxy-N,N-bis(2-methoxyethyl)-6-[3-methoxy-4-[2-(4-morpholinyl)ethoxy]benzoyl]- KW-2478 |
Description | KW-2478 is an inhibitor of Hsp90α, with an IC50 of 3.8 nM, and has antitumor activity against various human hematological tumor cells. |
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Related Catalog | |
Target |
HSP90α:3.8 nM (IC50) |
In Vitro | KW-2478 is an inhibitor of Hsp90, with an IC50 of 3.8 nM for Hsp90α. KW-2478 shows anti-proliferative activity against multiple myeloma (MM) and non-Hodgkin’s lymphoma (NHL), with GI50s of 0.30 μM (OPM-2/GFP), 0.34 μM (KMS-11), 0.39 μM (RPMI 8226), 0.12 μM (NCI-H929), 0.36 μM (Raji), 0.098 μM (SR), and 0.33 μM μM (SC-1). KW-2478 also inhibits the transcription of c-Maf and Cyclin D1 genes by mainly suppressing the function of Cdk9[1]. |
In Vivo | KW-2478 (25-200 mg/kg, i.v.) inhibits tumor growth in combined immunodeficiency (SCID) mice bearing NCI-H929 cells, without body weight loss. KW-2478 (100 mg/kg, i.v.) causes degradation of the Hsp90 client proteins (IGF-1Rβ, c-Raf-1, Cdk9) levels and dephosphorylated Erk1/2 proteins in NCI-H929 tumors of mice[1]. |
Cell Assay | The cells are plated into 96-well plates and treated with KW-2478. After 72 hours of cultivation, cell viability is determined using 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[1]. |
Animal Admin | Mice[1] Severe combined immunodeficient (SCID) mice are intraperitoneally injected with anti-asialo GM1 antibody. The next day, all mice are subcutaneously inoculated with NCI-H929 cells (1×107 cells) suspended in PBS containing 50% of Matrigel. After 10 days, tumor volume is measured using the Antitumor test system II, a computer-operated system including software and instruments. SCID mice with tumors (190 to 290 mm3) are selected. After randomly grouping, saline (vehicle) or KW-2478 is intravenously administered to mice once or twice daily for 5 days. 17-AAG is intravenously administered to mice. Tumor volume is calculated by the Anti-tumor test system II as follows: Tumor volume=DL×DS×DS×1/2. Fourteen days after the initial administration, blood samples of each mouse are obtained, followed by measurement of serum M protein (Ig kappa chain) with Human Kappa-b&f ELISA Quantitation Kit. The statistical analysis is performed using SAS software[1]. |
References |
Density | 1.2±0.1 g/cm3 |
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Boiling Point | 746.9±60.0 °C at 760 mmHg |
Molecular Formula | C30H42N2O9 |
Molecular Weight | 574.662 |
Flash Point | 405.5±32.9 °C |
Exact Mass | 574.289001 |
PSA | 127.23000 |
LogP | 2.99 |
Vapour Pressure | 0.0±2.6 mmHg at 25°C |
Index of Refraction | 1.560 |
Storage condition | -20℃ |