KW-2478

• CAT Number: I007541
• CAS Number: 819812-04-9
• Molecular Formula: C30H42N2O9
• Molecular Weight: 574.671
• Purity: ≥95%
• Target: HSP
• Solubility: Soluble in DMSO, not soluble in water.
• Storage: 3 years -20C powder
• Related CAS: 819812-18-5(hydrochloride)
• IUPAC Name: 2-[2-ethyl-3,5-dihydroxy-6-[3-methoxy-4-(2-morpholin-4-ylethoxy)benzoyl]phenyl]-N,N-bis(2-methoxyethyl)acetamide
• 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
• InChIKey: VFUXSYAXEKYYMB-UHFFFAOYSA-N
• SMILES: CCC1=C(C=C(C(=C1CC(=O)N(CCOC)CCOC)C(=O)C2=CC(=C(C=C2)OCCN3CCOCC3)OC)O)O

KW-2478(CAT: I007541) 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. HSP90 is a molecular chaperone that plays a key role in the conformational maturation of oncogenic signaling proteins, such as HER2/ERBB2, AKT, RAF1, BCR-ABL, and mutated p53, as well as many other molecules that are important in cell cycle regulation or immune responses.

Reference

1: Yong K, Cavet J, Johnson P, Morgan G, Williams C, Nakashima D, Akinaga S,
Oakervee H, Cavenagh J. Phase I study of KW-2478, a novel Hsp90 inhibitor, in
patients with B-cell malignancies. Br J Cancer. 2016 Jan 12;114(1):7-13. doi:
10.1038/bjc.2015.422. Epub 2015 Dec 22. PubMed PMID: 26695442; PubMed Central
PMCID: PMC4716540.

2: 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.

3: 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.