WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 205506
CAS#: 819812-04-9 (free base)
Description: KW-2478 is an agent that targets the human heat-shock protein 90 (Hsp90) with potential antineoplastic activity. Although the mechanism of action remains to be fully elucidated, Hsp90 antagonist KW-2478 appears to inhibit Hsp90, resulting in impaired signal transduction, inhibition of cell proliferation, and the induction of apoptosis in tumor cells.
MedKoo Cat#: 205506
Name: KW-2478 free base
CAS#: 819812-04-9 (free base)
Chemical Formula: C30H42N2O9
Exact Mass: 574.28903
Molecular Weight: 574.66248
Elemental Analysis: C, 62.70; H, 7.37; N, 4.87; O, 25.06
Related CAS #: 819812-18-5 (HCl) 819812-04-9 (free base)
Synonym: KW2478; KW-2478; KW 2478.
IUPAC/Chemical Name: 2-(2-ethyl-3,5-dihydroxy-6-(3-methoxy-4-(2-morpholinoethoxy)benzoyl)phenyl)-N,N-bis(2-methoxyethyl)acetamide
InChi Key: VFUXSYAXEKYYMB-UHFFFAOYSA-N
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
SMILES Code: O=C(N(CCOC)CCOC)CC1=C(C(C2=CC=C(OCCN3CCOCC3)C(OC)=C2)=O)C(O)=CC(O)=C1CC
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years)
Solubility: Soluble in DMSO, not soluble in water.
Shelf Life: >5 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
The following data is based on the product molecular weight 574.66248 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||1.15 mL||5.76 mL||11.51 mL|
|5 mM||0.23 mL||1.15 mL||2.3 mL|
|10 mM||0.12 mL||0.58 mL||1.15 mL|
|50 mM||0.02 mL||0.12 mL||0.23 mL|
1: Soga S. [Drug discovery and research of heat shock protein 90 (Hsp90) inhibitor]. Nihon Yakurigaku Zasshi. 2013 Jan;141(1):9-14. Review. Japanese. PubMed PMID: 23302942.
2: Soga S, Akinaga S, Shiotsu Y. Hsp90 inhibitors as anti-cancer agents, from basic discoveries to clinical development. Curr Pharm Des. 2013;19(3):366-76. Review. PubMed PMID: 22920907.
3: Ishii T, Seike T, Nakashima T, Juliger S, Maharaj L, Soga S, Akinaga S, Cavenagh J, Joel S, Shiotsu Y. Anti-tumor activity against multiple myeloma by combination of KW-2478, an Hsp90 inhibitor, with bortezomib. Blood Cancer J. 2012 Apr;2(4):e68. doi: 10.1038/bcj.2012.13. Epub 2012 Apr 27. PubMed PMID: 22829970; PubMed Central PMCID: PMC3346683.
4: 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 May 15;16(10):2792-802. doi: 10.1158/1078-0432.CCR-09-3112. Epub 2010 Apr 20. PubMed PMID: 20406843.
Research from Japan recently reported 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. (Clin Cancer Res. 2010 May 15;16(10):2792-802. ).
Research from Japan recently reported that