WEHI-539

製品コードS7100 バッチS710001

印刷

化学情報

Synonyms

Storage
(From the date of receipt)

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

化学式

C₃₁H₂₉N₅O₃S₂

分子量

583.73

CAS No.

1431866-33-9

Solubility (25°C)*

体外

DMSO

100 mg/mL (171.31 mM)

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.

* <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	WEHI-539は、BCL-XLに対し高い親和性（IC50=1.1 nM）と選択性を持ち、その生存促進活性を選択的に阻害することで強力に細胞を殺傷します。他の生存促進性BCL-2ファミリーメンバーと比較して、BCL-XLに対する親和性は400倍以上高いです。
in vitro	WEHI-539 shows good selectivity for BCL-XL. The tight ligand of this compound retains this selectivity (500-fold over BCL-2 and 400-fold over BCL-W, MCL-1 and A1). It kills fibroblasts that lack MCL-1. Thus, this compound not only binds very tightly to BCL-XL, with IC50 and KD values close to or below 1 nM as well as a slow dissociation rate, but also invokes apoptotic responses that depend on BAX, BAK or both; furthermore, its biological activity is related to its binding profile, as elevated amounts of MCL-1, BCL-2 and BCL-W confer marked resistance, and its ability to destroy platelets is a well-validated marker of on-target BCL-XL inhibition. In addition, this chemical induces a preferentially BAK-dependent apoptotic response in MEFs by selectively inhibiting BCL-XL.

製品説明

WEHI-539は、BCL-XLに対し高い親和性（IC50=1.1 nM）と選択性を持ち、その生存促進活性を選択的に阻害することで強力に細胞を殺傷します。他の生存促進性BCL-2ファミリーメンバーと比較して、BCL-XLに対する親和性は400倍以上高いです。

in vitro

WEHI-539 shows good selectivity for BCL-XL. The tight ligand of this compound retains this selectivity (500-fold over BCL-2 and 400-fold over BCL-W, MCL-1 and A1). It kills fibroblasts that lack MCL-1. Thus, this compound not only binds very tightly to BCL-XL, with IC50 and KD values close to or below 1 nM as well as a slow dissociation rate, but also invokes apoptotic responses that depend on BAX, BAK or both; furthermore, its biological activity is related to its binding profile, as elevated amounts of MCL-1, BCL-2 and BCL-W confer marked resistance, and its ability to destroy platelets is a well-validated marker of on-target BCL-XL inhibition. In addition, this chemical induces a preferentially BAK-dependent apoptotic response in MEFs by selectively inhibiting BCL-XL.

プロトコル(参考用のみ)

キナーゼアッセイ	AlphaScreen assay
キナーゼアッセイ	The assay buffer (stock 50 mM HEPES and 100 mM NaCl, pH 7.5) is prepared fresh daily and adjusted to 5 mM DTT, casein (0.1 mg/mL sodium salt; aliquots stored at -20 °C) and Tween 20 such that the
細胞アッセイ	細胞株	MEFs
	濃度	10 μM
	反応時間	1 h
	実験の流れ	Wild-type (WT), mcl-1^−/−, bcl-2^−/− or bcl-x^−/− MEFs were treated with 10 μM WEHI-539 or ABT-737 for 1 h and fractionated into mitochondrial-enriched (pellet) and cytosolic (soluble) fractions, which were subjected to SDS-PAGE and immunoblotted with antibody against cytochrome c (anti-cyt c); HSP70 was used as a loading control.

参考

https://pubmed.ncbi.nlm.nih.gov/23603658/

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：

Multi-selective RAS(ON) Inhibition Targets Oncogenic RAS Mutations and Overcomes RAS/MAPK-Mediated Resistance to FLT3 and BCL2 Inhibitors in Acute Myeloid Leukemia [ bioRxiv, 2025, 2025.06.10.658786]	PubMed: 40661530
Allosteric SHP2 inhibition increases apoptotic dependency on BCL2 and synergizes with venetoclax in FLT3- and KIT-mutant AML [ Cell Rep Med, 2023, 4(11):101290]	PubMed: 37992684
Exploiting ulnerabilities induced b recurrent mutations in chondrosarcoma and giant cell tumour of bone: therapeutic targeting of the altered epigenome and be [ Leiden University The Netherlands, 2023, ]	PubMed: None
Bcl-xL as prognostic marker and potential therapeutic target in cholangiocarcinoma [ Liver Int, 2022, 10.1111/liv.15392]	PubMed: 35983950
BCL-XL is crucial for progression through the adenoma-to-carcinoma sequence of colorectal cancer [ Cell Death Differ, 2021, 10.1038/s41418-021-00816-w]	PubMed: 34117376
Age-related injury responses of human oligodendrocytes to metabolic insults: link to BCL-2 and autophagy pathways [ Commun Biol, 2021, 4(1):20]	PubMed: 33398046
Identification des voies de signalisations impliquées dans l'activité pro-apoptotique du récepteur à dépendance UNC5B [ HAL open science, 2021, version 1]	PubMed: None
CDK5 Inhibitor Downregulates Mcl-1 and Sensitizes Pancreatic Cancer Cell Lines to Navitoclax [ Mol Pharmacol, 2019, 96(4):419-429]	PubMed: 31467029
Intracellular BH3 Profiling Reveals Shifts in Antiapoptotic Dependency in Human B Cell Maturation and Mitogen-Stimulated Proliferation [Dai J J Immunol, 2018, 200(5):1727-1736]	PubMed: 29358277
Myeloid cell leukemia-1 is an important apoptotic survival factor in triple-negative breast cancer [Goodwin CM Cell Death Differ, 2015, 22(12):2098-106]	PubMed: 26045046

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。