WEHI-539

Catalog No.S7100 Batch:S710001

Technical Data

Formula	C₃₁H₂₉N₅O₃S₂
Molecular Weight	583.73	CAS No.	1431866-33-9
Solubility (25°C)*	In vitro	DMSO	100 mg/mL (171.31 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. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description

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.

Targets

Bcl-xL ^[1]
(Cell-free assay)

1.1 nM

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].

Protocol (from reference)

Kinase Assay:^{^[1]}	AlphaScreen assay 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
Cell Assay:^{^[1]}	Cell lines MEFs Concentrations 10 μM Incubation Time 1 h Method 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.

Kinase Assay:^{^[1]}

AlphaScreen assay
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

Cell Assay:^{^[1]}

Cell lines
MEFs
Concentrations
10 μM
Incubation Time
1 h
Method
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.

References

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

Selleck's WEHI-539 has been cited by 8 publications

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

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.