WEHI-539

Catalog No.S7100

WEHI-539 Chemical Structure

Molecular Weight(MW): 620.18

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.

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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

Kinase Assay:

[1]

+ Expand

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 Research:

[1]

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  • 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.


    (Only for Reference)

Solubility (25°C)

In vitro DMSO 100 mg/mL (161.24 mM)

* 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.

Chemical Information

Molecular Weight 620.18
Formula

C31H29N5O3S2.HCl

CAS No. 2070018-33-4
Storage powder
in solvent
Synonyms N/A

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Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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Bcl-2 Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID