KW-2478

製品コードS2685 バッチS268502

印刷

化学情報

Synonyms

N/A

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₃₀H₄₂N₂O₉

分子量

574.66

CAS No.

819812-04-9

Solubility (25°C)*

体外

DMSO

115 mg/mL (200.11 mM)

Ethanol

3 mg/mL (5.22 mM)

Water

Insoluble

体内（毎回新しく調製した物を用意してください）

Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	30%propylene glycol 1 5%Tween80 2 65%D5W この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	10.000mg/ml (17.40mM)	Taking the 1 mL working solution as an example, add 300 μL of 33.33 mg/ml clarified propylene glycol stock solution to 50 μL of Tween 80, mix evenly to clarify it; then continue to add 650 μL of D5W to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	KW-2478 is a nonansamycin HSP90 inhibitor with IC50 of 3.8 nM. Phase 1.
in vitro	KW-2478 inhibits the binding of bRD to Hsp90α with IC50 of 3.8 nM. This compound degradates the Hsp90 client proteins, including FGFR3 and IGF-1Rβand c-Raf-1. It reduces the level of phosphorylated Erk1/2. This chemical induces apoptosis by cleavage of PARP, a substrate of caspase-3 In U266 cells,. It has Time dependency of antiproliferative activity, consecutive drug exposure for at least 12 hours is necessary to to exert potent antitumor activity. This agent downregulates the translocation products of IgH locus. It inhibits the transcription of c-Maf and cyclin D1 genes by mainly suppressing the function of Cdk9. ^[1] This compound has potent and broad growth inhibitory activities against various cell lines, it 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. It also shows potent growth inhibitory activity in primary CLL and NHL cells with EC50 of 40-170 nM and 200-400 nM, respectively. ^[2].
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. This compound 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]

プロトコル(参考用のみ)

キナーゼアッセイ	Hsp90 Binding Assay
キナーゼアッセイ	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.
細胞アッセイ	細胞株	OPM-2/GFP, KMS-11, RPMI 8226, and NCI-H929 cells
	濃度	0.05 - 5 μM
	反応時間	3 days
	実験の流れ	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 this compound, the cells are plated into 96-well V-bottomed plates and treated with this chemical. 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
動物実験	動物モデル	NCI-H929 tumors s.c. inoculated in SCID mice, OPM-2/GFP i.v. inoculated mouse model
	投薬量	25, 50 , 100 and 200 mg/kg
	投与方法	Orally administrated once daily for 5 days

参考

https://pubmed.ncbi.nlm.nih.gov/20406843/
http://ash.confex.com/ash/2008/webprogram/Paper7755.html
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3346683

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Nidogen-1, a Player in KMT2A-Rearranged Pediatric Acute Myeloid Leukemia [ Int J Mol Sci, 2025, 26(7)3011]	PubMed: 40243655
Inhibition of HSP90 overcomes melphalan resistance through downregulation of Src in multiple myeloma cells. [ Clin Exp Med, 2019, 10.1007/s10238-019-00587-2]	PubMed: 31650359

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。