- 貨號 Cat. No.
- S2685
- 規格 Size
- 5~200mg
- 品牌 Brand
- Selleckchem
Description
KW-2478
Catalog No.S2685
KW-2478 is a nonansamycin HSP90 inhibitor with IC50 of 3.8 nM. Phase 1/2
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10mM/1mLIn DMSO |
USD 781 |
In stock |
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5mg |
USD 340 |
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10mg |
USD 466 |
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50mg |
USD 1222 |
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200mg |
USD 3364 |
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
Description |
KW-2478 is a nonansamycin HSP90 inhibitor with IC50 of 3.8 nM. Phase 1/2 |
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Targets |
HSP90 |
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IC50 |
3.8 nM [1] |
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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]. |
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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] |
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Features |
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Protocol(Only for Reference)
Kinase Assay: [1]
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. |
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Cell Assay: [1]
Cell lines |
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. |
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Concentrations |
0.05 - 5 μM |
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Incubation Time |
3 days |
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Method |
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 |
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Animal Study: [1]
Animal Models |
NCI-H929 tumors s.c. inoculated in SCID mice, OPM-2/GFP i.v. inoculated mouse model |
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Dosages |
25, 50 , 100 and 200 mg/kg |
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Administration |
Orally administrated once daily for 5 days |
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Solubility |
30% propylene glycol, 5% Tween 80, 65% D5W, 10 mg/mL |
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1
References
Clinical Trial Information( data from http://clinicaltrials.gov)
NCT Number |
Recruitment |
Conditions |
Sponsor
/Collaborators |
Start Date |
Phases |
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NCT00457782 |
Completed |
Multiple Myeloma|Chronic Lymphocytic Leukaemia|Lymphoma, B-Cell |
Kyowa Hakko Kirin Pharma, Inc.|Kyowa Hakko Kirin UK, Ltd. |
2007-04 |
Phase 1 |
NCT01063907 |
Active, not recruiting |
Multiple Myeloma |
Kyowa Hakko Kirin Pharma, Inc.|Kyowa Hakko Kirin Company, Limited |
2010-03 |
Phase 1|Phase 2 |
Download KW-2478 SDF
Molecular Weight (MW) |
574.66 |
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Formula |
C30H42N2O9
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CAS No. |
819812-04-9 |
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Storage |
3 years -20℃Powder |
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6 months-80℃in DMSO |
Syonnyms |
N/A |
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Solubility (25°C) * |
In vitro |
DMSO |
115 mg/mL (200 mM) |
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Water |
<1 mg/mL (<1 mM) |
Ethanol |
3 mg/mL (5 mM) |
In vivo |
30% propylene glycol, 5% Tween 80, 65% D5W, |
10 mg/mL |
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
Chemical Name |
2-(2-ethyl-3,5-dihydroxy-6-(3-methoxy-4-(2-morpholinoethoxy)benzoyl)phenyl)-N,N-bis(2-methoxyethyl)acetamide |
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Stock Solution (1ml DMSO) |
1mM |
10mM |
20mM |
30mM |
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Mass(mg) |
0.57466 |
5.7466 |
11.4932 |
17.2398 |
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