KW-2478 | CAS#819812-04-9 | HSP90 inhibitor

MedKoo Cat#: 205506 | Name: KW-2478 free base

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

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.

Chemical Structure

KW-2478 free base

CAS#819812-04-9 (free base)

Theoretical Analysis

MedKoo Cat#: 205506

Name: KW-2478 free base

CAS#: 819812-04-9 (free base)

Chemical Formula: C30H42N2O9

Exact Mass: 574.2890

Molecular Weight: 574.67

Elemental Analysis: C, 62.70; H, 7.37; N, 4.87; O, 25.06

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 410.00	2 Weeks
10mg	USD 750.00	2 Weeks

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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

More Info

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

Product Data

Product Data

Instruction

View handling instruction

Biological target:

KW-2478 is an inhibitor of Hsp90α, with an IC50 of 3.8 nM, and has antitumor activity against various human hematological tumor cells.

In vitro activity:

Additionally, KW-2478 exhibited favorable anti-NSCLC activity in vitro, as it inhibited cell proliferation (IC50, 8.16 μM for A549; 14.29 μM for H1975) and migration, induced cell cycle arrest and promoted apoptosis. Reference: J Struct Biol. 2021 Jun;213(2):107710. https://pubmed.ncbi.nlm.nih.gov/33610655/

In vivo activity:

Notably, KW-2478 had a stronger effect on growth inhibition, apoptosis induction and cell cycle arrest of K562/G01 cells than K562 cells. KW-2478 could effectively prolong the mouse lifespan and alleviate disease symptoms in CML-like mouse models. Reference: Exp Hematol Oncol. 2022 May 27;11(1):33. https://pubmed.ncbi.nlm.nih.gov/35624462/

	Solvent	mg/mL	mM
Solubility
	DMF	5.0	8.70
	DMSO	106.7	185.61
	DMSO:PBS (pH 7.2) (1:7)	0.1	0.22

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 574.67 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

Formulation protocol:

1. Li HJ, Wang QS, Han W, Zhou H, Li P, Zhou F, Qin W, Zhao D, Zhou X, He CX, Xing L, Li PQ, Jin X, Yu F, He JH, Cao HL. Anti-NSCLC activity in vitro of Hsp90N inhibitor KW-2478 and complex crystal structure determination of Hsp90N-KW-2478. J Struct Biol. 2021 Jun;213(2):107710. doi: 10.1016/j.jsb.2021.107710. Epub 2021 Feb 19. PMID: 33610655. 2. Tabata M, Tsubaki M, Takeda T, Tateishi K, Maekawa S, Tsurushima K, Imano M, Satou T, Ishizaka T, Nishida S. Inhibition of HSP90 overcomes melphalan resistance through downregulation of Src in multiple myeloma cells. Clin Exp Med. 2020 Feb;20(1):63-71. doi: 10.1007/s10238-019-00587-2. Epub 2019 Oct 24. PMID: 31650359. 3. Zeng D, Gao M, Zheng R, Qin R, He W, Liu S, Wei W, Huang Z. The HSP90 inhibitor KW-2478 depletes the malignancy of BCR/ABL and overcomes the imatinib-resistance caused by BCR/ABL amplification. Exp Hematol Oncol. 2022 May 27;11(1):33. doi: 10.1186/s40164-022-00287-w. PMID: 35624462; PMCID: PMC9137153. 4. 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. PMID: 22829970; PMCID: PMC3346683.

In vitro protocol:

In vivo protocol:

1. Zeng D, Gao M, Zheng R, Qin R, He W, Liu S, Wei W, Huang Z. The HSP90 inhibitor KW-2478 depletes the malignancy of BCR/ABL and overcomes the imatinib-resistance caused by BCR/ABL amplification. Exp Hematol Oncol. 2022 May 27;11(1):33. doi: 10.1186/s40164-022-00287-w. PMID: 35624462; PMCID: PMC9137153. 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. PMID: 22829970; PMCID: PMC3346683.

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.