WEHI-539

製品コードS7100 バッチS710001

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	620.18	CAS No.	1431866-33-9
Solubility (25°C)*	体外	DMSO	100 mg/mL (161.24 mM)


* <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 has high affinity (IC50=1.1 nM) and selectivity for BCL-XL and potently kills cells by selectively antagonizing its prosurvival activity. It has more than a 400-fold higher affinity for BCL-XL versus other prosurvival BCL-2 family members.
in vitro	WEHI-539 shows good selectivity for BCL-XL. The tight ligand WEHI-539 retains this selectivity (500-fold over BCL-2 and 400-fold over BCL-W, MCL-1 and A1). WEHI-539 kills fibroblasts that lack MCL-1. Thus, WEHI-539 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, WEHI-539 induces a preferentially BAK-dependent apoptotic response in MEFs by selectively inhibiting BCL-XL^[1].

製品説明

WEHI-539 has high affinity (IC50=1.1 nM) and selectivity for BCL-XL and potently kills cells by selectively antagonizing its prosurvival activity. It has more than a 400-fold higher affinity for BCL-XL versus other prosurvival BCL-2 family members.

in vitro

WEHI-539 shows good selectivity for BCL-XL. The tight ligand WEHI-539 retains this selectivity (500-fold over BCL-2 and 400-fold over BCL-W, MCL-1 and A1). WEHI-539 kills fibroblasts that lack MCL-1. Thus, WEHI-539 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, WEHI-539 induces a preferentially BAK-dependent apoptotic response in MEFs by selectively inhibiting BCL-XL^[1].

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

[1] Lessene G, et al. Nat Chem Biol, 2013, 9(6), 390-397.

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：

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
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
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
RAS signaling promotes resistance to JAK inhibitors by suppressing BAD-mediated apoptosis [ Sci Signal, 2014, 7(357):ra122]	PubMed: 25538080

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。

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