WEHI-539 is a small-molecule inhibitor of BCLXLwith an IC50 value of 1.1 nM .
WEHI-539 was designed as a BCL-XLinhibitor with high affinity. It interacted the with the binding groove of BCL-XLwith a Kd value of 0.6 nM. In MEF cells lacking MCL-1, WEHI-539 induced apoptosis which was evidenced by the release of mitochondrial cytochrome cand caspase-3 processing. In BCL-XLoverexpressed MEF cells, WEHI-539 showed EC50 value of 0.48 μM. WEHI-539 also significantly induced apoptosis of the platelets purified from mice. Besides that, WEHI-539can not kill MEF cells lacking BAK because the cell death mediator BAK is regulated by BCL-XLand MCL-1. .
 Lessene G, Czabotar P E, Sleebs B E, et al. Structure-guided design of a selective BCL-XL inhibitor. Nature chemical biology, 2013, 9(6): 390-397.
- 1. de Jong Y, Monderer D, et al. "Bcl-xl as the most promising Bcl-2 family member in targeted treatment of chondrosarcoma." Oncogenesis. 2018 Sep 21;7(9):74. PMID:30242253
- 2. Soderquist RS, Crawford L, et al. "Systematic mapping of BCL-2 gene dependencies in cancer reveals molecular determinants of BH3 mimetic sensitivity." Nat Commun. 2018 Aug 29;9(1):3513. PMID:30158527
- 3. Wilson Xuan Mai."Comprehensive Characterization of the Apoptotic Machinery in Glioblastoma Identifies New Therapeutic Strategies." UNIVERSITY OF CALIFORNIA.2018-01-01.
- 4. Dai J, Luftig MA. "Intracellular BH3 Profiling Reveals Shifts in Antiapoptotic Dependency in Human B Cell Maturation and Mitogen-Stimulated Proliferation." J Immunol. 2018 Mar 1;200(5):1727-1736. PMID:29358277
- 5. Vuillier C, Lohard S, et al. "E2F1 interacts with BCL-xL and regulates its subcellular localization dynamics to trigger cell death." EMBO Rep. 2017 Dec 12. PMID:29233828
- 6. Mai WX, Gosa L, et al. "Cytoplasmic p53 couples oncogene-driven glucose metabolism to apoptosis and is a therapeutic target in glioblastoma." Nat Med. 2017 Nov;23(11):1342-1351. PMID:29035366
- 7. Park HA, Licznerski P, et al. "Inhibition of Bcl-xL prevents pro-death actions of ΔN-Bcl-xL at the mitochondrial inner membrane during glutamate excitotoxicity."Cell Death Differ. 2017 Nov;24(11):1963-1974. PMID:28777375
- 8. Tan Y, Lin Y, et al. "Selective Antagonism of Bcl-xL Potentiates M1 Oncolysis by Enhancing Mitochondrial Apoptosis." Hum Gene Ther. 2017 Jul 27. PMID:28750564
- 9. Rose JC, Stephany JJ, et al. "Rapidly inducible Cas9 and DSB-ddPCR to probe editing kinetics." Nat Methods. 2017 Sep;14(9):891-896. PMID:28737741
- 10. Russo M, Milito A, et al. "CK2 and PI3K are direct molecular targets of quercetin in chronic lymphocytic leukaemia." Oncotarget. 2017 Jun 27;8(26):42571-42587. PMID:28489572
- 11. Bi C, Zhang X, et al."Inhibition of 4EBP phosphorylation mediates the cytotoxic effect of mechanistic target of rapamycin kinase inhibitors in aggressive B-cell lymphomas."Haematologica. 2017 Apr;102(4):755-764. PMID:28104700
- 12. Pécot J, Maillet L, et al. "Tight Sequestration of BH3 Proteins by BCL-xL at Subcellular Membranes Contributes to Apoptotic Resistance." Cell Rep. 2016 Dec 20;17(12):3347-3358. PMID:28009301
- 13. Bennett A, Sloss O, et al. "Inhibition of Bcl-xL sensitizes cells to mitotic blockers, but not mitotic drivers." Open Biol. 2016 Aug;6(8). PMID:27512141
- 14. Kris Cameron Wood,Peter Saville Winter. "Compositions and Methods for Treating Cancer with JAK2 Activity." US Patent App. 15/027,216, 2016.
- 15. Winter PS, et al. "RAS signaling promotes resistance to JAK inhibitors by suppressing BAD-mediated apoptosis." Sci Signal. 2014 Dec 23. PMID:25538080
|Physical Appearance||A solid|
|Storage||Store at -20°C|
|Solubility||<1.17 mg/mL in DMSO, <2.44 mg/mL in EtOH, <2.24 mg/mL in H2O|
|Chemical Name||5-[3-[4-(aminomethyl)phenoxy]propyl]-2-[(8E)-8-(1,3-benzothiazol-2-ylhydrazinylidene)-6,7-dihydro-5H-naphthalen-2-yl]-1,3-thiazole-4-carboxylic acid|
|Shipping Condition||Evaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request|
|General tips||For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.|
Human colon cancer cell
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.
1 μM, 24h
Limiting dilution analysis with CSCs that were pre-treated with ABT-737, ABT-199 or WEHI-539 revealed that ABT-737 and WEHI-539 both were sufficient to decrease clonogenic capacity, whereas ABT-199 did not affect clonogenic growth. As WEHI-539 is selective for BCLXL, this points to a dependency of CSCs on BCLXL for survival. Importantly, ABT-737- or WEHI-539-induced loss of clonogenicity could be restored when BCLXL was ectopically overexpressed. When spheroid cultures were treated with ABT-737 or WEHI-539 compounds, CSCs were effectively sensitized toward oxaliplatin and other chemotherapeutic agents.
1. Colak S, Zimberlin CD, Fessler E et al. Decreased mitochondrial priming determines chemoresistance of colon cancer stem cells. Cell Death Differ. 2014 Jul;21(7):1170-7.
|WEHI-539, has high affinity (subnanomolar) and selectivity for BCL-XL and potently kills cells by selectively antagonizing its prosurvival activity. WEHI-539 has a high affinity for BCL-XL (IC50 = 1.1 nM).|
Quality Control & MSDS
- View current batch: