KW-2478Potent Hsp90 inhibitor, novel, non-ansamycin, CAS# 819812-04-9 |
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Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
| Cas No. | 819812-04-9 | SDF | Download SDF |
| PubChem ID | 23116322 | Appearance | Powder |
| Formula | C30H42N2O9 | M.Wt | 574.66 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO : ≥ 83.3 mg/mL (144.96 mM) *"≥" means soluble, but saturation unknown. | ||
| Chemical Name | 2-[2-ethyl-3,5-dihydroxy-6-[3-methoxy-4-(2-morpholin-4-ylethoxy)benzoyl]phenyl]-N,N-bis(2-methoxyethyl)acetamide | ||
| SMILES | CCC1=C(C=C(C(=C1CC(=O)N(CCOC)CCOC)C(=O)C2=CC(=C(C=C2)OCCN3CCOCC3)OC)O)O | ||
| Standard InChIKey | VFUXSYAXEKYYMB-UHFFFAOYSA-N | ||
| Standard InChI | 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 | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | KW-2478 is a novel, non-ansamycin, potent inhibitor of Hsp90 with IC50 value of 3.8 nM. | |||||
| Targets | Hsp90 | |||||
| IC50 | 3.8 nM | |||||
KW-2478 Dilution Calculator
KW-2478 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 1.7402 mL | 8.7008 mL | 17.4016 mL | 34.8032 mL | 43.504 mL |
| 5 mM | 0.348 mL | 1.7402 mL | 3.4803 mL | 6.9606 mL | 8.7008 mL |
| 10 mM | 0.174 mL | 0.8701 mL | 1.7402 mL | 3.4803 mL | 4.3504 mL |
| 50 mM | 0.0348 mL | 0.174 mL | 0.348 mL | 0.6961 mL | 0.8701 mL |
| 100 mM | 0.0174 mL | 0.087 mL | 0.174 mL | 0.348 mL | 0.435 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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KW-2478 is a novel and potent nonansamycin inhibitor of heat shock protein 90 (Hsp90) to overcome the limitations, including low water solubility and hepatotoxicity, of 17-allylamino-17-demethoxygeldanamycin (17-AAG). KW-2478 exerts a strong antitumor activity against multiple myeloma (MM) cells with various chromosormal translocation, in which KW-2478 inhibits cell growth and apoptosis associated with Hsp90 client protein degradation and the decreasing of IgH translocation products including FGFR3, c-Maf and cyclin D1. Recent study results have revealed that KW-2478 is able to deplete Hsp90 client Cdk9 and the phosphorylated 4E-BP1, a transcriptional kinase and a transcription inhibitor respectively, leading to the reduced expression of c-Maf and cyclin D1.
Reference
Nakashima T, Ishii T, Tagaya H, Seike T, Nakagawa H, Kanda Y, Akinaga S, Soga S, Shiotsu Y. New molecular and biological mechanism of antitumor activities of KW-2478, a novel nonansamycin heat shock protein 90 inhibitor, in multiple myeloma cells. Clin Cancer Res. 2010; 16(10): 2792-802.
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Phase I study of KW-2478, a novel Hsp90 inhibitor, in patients with B-cell malignancies.[Pubmed:26695442]
Br J Cancer. 2016 Jan 12;114(1):7-13.
BACKGROUND: KW-2478 is a novel, non-ansamycin, non-purine heat-shock protein 90 (Hsp90) inhibitor. METHODS: In this phase I, multicentre study, KW-2478 was administered intravenously over 1 h at doses ranging from 14 to 176 mg m(-2) once daily on days 1-5 of a 14-day cycle in a standard 3+3 design in 27 patients (22 with multiple myeloma and 5 with non-Hodgkin lymphoma). Patients enrolled had relapsed/refractory disease previously treated with 2 regimens. RESULTS: There were no dose-limiting toxicities, thus the maximum-tolerated dose was not reached. KW-2478 was well tolerated and did not manifest significant retinal or ocular toxicity. The most common treatment-related adverse events were diarrhoea (33.3%), fatigue (29.6%), headache (25.9%), hypertension (22.2%), nausea (14.8%), vomiting (7.4%), and dizziness (7.4%). Plasma concentrations peaked at the end of infusion and decayed in a biphasic manner with a terminal half-life of approximately 6 h. Target inhibition was inferred from the increase in Hsp70 levels in peripheral blood mononuclear cells at doses 71 mg m(-2). Twenty-four of 25 (96%) evaluable patients showed stable disease, with five being free of disease progression for 6 months. CONCLUSIONS: Preliminary clinical response data were encouraging and warrant further investigation of KW-2478 in combination regimens for relapsed/refractory B-cell malignancies.
New molecular and biological mechanism of antitumor activities of KW-2478, a novel nonansamycin heat shock protein 90 inhibitor, in multiple myeloma cells.[Pubmed:20406843]
Clin Cancer Res. 2010 May 15;16(10):2792-802.
PURPOSE: The heat shock protein 90 (Hsp90) plays an important role in chaperoning oncogenic client proteins in multiple myeloma (MM) cells, and several Hsp90 inhibitors have shown antitumor activities both in vitro and in vivo. However the precise mechanism of action of Hsp90 inhibitor in MM has not been fully elucidated. EXPERIMENTAL DESIGN: We evaluated the antitumor activities of KW-2478, a nonansamycin Hsp90 inhibitor, in MM cells with various chromosomal translocations of immunoglobulin heavy chain (IgH) loci both in vitro and in vivo. RESULTS: Our studies revealed that exposure of KW-2478 to MM cells resulted in growth inhibition and apoptosis, which were associated with degradation of well-known client proteins as well as a decrease in IgH translocation products (FGFR3, c-Maf, and cyclin D1), and FGFR3 was shown to be a new client protein of Hsp90 chaperon complex. In addition, KW-2478 depleted the Hsp90 client Cdk9, a transcriptional kinase, and the phosphorylated 4E-BP1, a translational inhibitor. Both inhibitory effects of KW-2478 on such transcriptional and translational pathways were shown to reduce c-Maf and cyclin D1 expression. In NCI-H929 s.c. inoculated model, KW-2478 showed a significant suppression of tumor growth and induced the degradation of client proteins in tumors. Furthermore, in a novel orthotopic MM model of i.v. inoculated OPM-2/green fluorescent protein, KW-2478 showed a significant reduction of both serum M protein and MM tumor burden in the bone marrow. CONCLUSIONS: These results suggest that targeting such diverse pathways by KW-2478 could be a promising strategy for the treatment of MM with various cytogenetic abnormalities.
Anti-tumor activity against multiple myeloma by combination of KW-2478, an Hsp90 inhibitor, with bortezomib.[Pubmed:22829970]
Blood Cancer J. 2012 Apr;2(4):e68.
Heat shock protein 90 (Hsp90) is a promising target for anti-tumor therapy. We previously reported the anti-tumor activity of a novel Hsp90 inhibitor, KW-2478, in multiple myeloma (MM) as a single agent. In this study, we examined the combinational effect of KW-2478 and bortezomib, a proteasome inhibitor, in vitro and in vivo. In vitro, KW-2478 enhanced bortezomib-induced cell growth inhibition, both in MM cell lines and primary patient MM cells. The combination of KW-2478 and bortezomib also induced caspase activation in MM cell lines. Interestingly, the combination synergistically enhanced the expression of Hsp70B, a homolog of Hsp70, in human MM cells and peripheral blood mononuclear cells, indicating Hsp70B could be a surrogate biomarker for the combination of Hsp90 and proteasome inhibitors. In vivo, the combination of KW-2478 with bortezomib showed synergistic anti-tumor activity without significant body weight loss in a subcutaneously inoculated human myeloma model. Furthermore, the combination also showed synergistic reduction of tumor burden in bone marrow in an orthotopic myeloma model. Our results strongly suggest that combination of KW-2478 with bortezomib could exhibit enhanced anti-tumor activity against human myeloma.
