WEHI-539
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
WEHI-539是BCLXL的小分子抑制剂,IC50值为1.1 nM [1]。
WEHI-539是一个高亲和性的BCLXL抑制剂,与BCL-XL的特定结构域相互作用,Kd值为0.6 nM。在缺乏MCL-1的MEF细胞中,WEHI-539诱导细胞凋亡,证据显示线粒体细胞色素C的释放和caspase-3的加工。在BCL-XL过表达的MEF细胞中,WEHI-539诱导细胞凋亡,EC50值为0.48 μM。
WEHI-539也可以显著诱导从小鼠中纯化的血小板细胞的凋亡。由于促凋亡调节蛋白BAK是由BCL-XL和MCL-1调控的,因此,WEHI-539不能诱导缺乏BAK的MEF细胞的凋亡[1]。
参考文献:
[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. Loo, Larry Sai Weng. "Dynamics of BCL-2 family of proteins in early pancreatic progenitors and β-cells." Nanyang Technological University.
- 2. Boccellato, Chiara, et al. "Overcoming glioblastoma intractability: pre-clinical characterisation of TRAIL sensitisation by marizomib and novel treatment perspectives." Universität Stuttgart. 2022.
- 3. Yasmeen A. Albalawi, Srinivas D. Narasipura, et al. "Wnt/β-Catenin Protects Lymphocytes from HIV-Mediated Apoptosis via Induction of Bcl-xL." Viruses. 2022 Jul 2;14(7):1469. PMID: 35891449
- 4. Kirsteen J. Campbell, Susan M. Mason, et al. "Breast cancer dependence on MCL-1 is due to its canonical anti-apoptotic function." Cell Death Differ. 2021 Sep;28(9):2589-2600. PMID: 33785871
- 5. Sanne Venneker, Alwine B. Kruisselbrink, et al. "Beyond the influence of idh mutations: Exploring epigenetic vulnerabilities in chondrosarcoma." Cancers (Basel). 2020 Nov 30;12(12):E3589. PMID: 33266275
- 6. Enyuan Shang, Trang T. T. Nguyen, et al. "Epigenetic Targeting of Mcl-1 Is Synthetically Lethal with Bcl-xL/Bcl-2 Inhibition in Model Systems of Glioblastoma." Cancers 2020, 12(8), 2137;1 August 2020. PMID: 32752193
- 7. Meyer L, Verbist KC, et al. "JAK/STAT pathway inhibition sensitizes CD8 T cells to dexamethasone-induced apoptosis in hyperinflammation." Blood. 2020;blood.2020006075. PMID: 32530039
- 8. Loo LSW, Soetedjo AAP, et al. "BCL-xL/BCL2L1 is a critical anti-apoptotic protein that promotes the survival of differentiating pancreatic cells from human pluripotent stem cells." Cell Death Dis. 2020;11(5):378. PMID: 32424151
- 9. Villalobos-Ortiz M, Ryan J, et al. "BH3 profiling discriminates on-target small molecule BH3 mimetics from putative mimetics." Cell Death Differ. 2019 Jul 22. PMID: 31332296
- 10. 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
- 11. 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
- 12. Wilson Xuan Mai."Comprehensive Characterization of the Apoptotic Machinery in Glioblastoma Identifies New Therapeutic Strategies." UNIVERSITY OF CALIFORNIA.2018-01-01.
- 13. 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
- 14. 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
- 15. 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
- 16. 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
- 17. 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
- 18. 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
- 19. 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
- 20. 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
- 21. 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
- 22. 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
- 23. Kris Cameron Wood,Peter Saville Winter. "Compositions and Methods for Treating Cancer with JAK2 Activity." US Patent App. 15/027,216, 2016.
- 24. 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 |
M.Wt | 583.72 |
Cas No. | 1431866-33-9 |
Formula | C31H29N5O3S2 |
Synonyms | WEHI539,WEHI 539 |
Solubility | insoluble in DMSO; insoluble in H2O; insoluble in EtOH |
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 |
SDF | Download SDF |
Canonical SMILES | C1CC2=C(C=C(C=C2)C3=NC(=C(S3)CCCOC4=CC=C(C=C4)CN)C(=O)O)C(=NNC5=NC6=CC=CC=C6S5)C1 |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。 |
细胞实验[1]: | |
细胞系 |
人结肠癌细胞 |
反应条件 |
1 μM;24 h |
应用 |
ABT-737、ABT-199或WEHI-539预处理肿瘤干细胞(CSCs)的有限稀释分析表明,ABT-737 和WEHI-539可以有效降低克隆能力,而ABT-199不影响克隆的生长。由于WEHI-539对BCLXL的选择性,表明CSCs的存活依赖于BCLXL。当BCLXL异位过表达时,ABT-737或WEHI-539诱导的克隆形成损失可以恢复。当球体细胞培养物用ABT-737或WEHI-539处理后,CSCs对oxaliplatin和其它的化疗药物变得敏感。 |
References: 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是一种高亲和性和选择性的BCL-XL抑制剂,IC50值为1.1 nM。WEHI-539通过选择性地拮抗BCL-XL的促生存活性从而有效杀死细胞。 | ||||||
靶点 | BCL-XL | |||||
IC50 | 1.1 nM |
质量控制和MSDS
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