VWK147
VWK147 is a second-generation HSP90 C-terminal domain (CTD) inhibitor. VWK147 targets the CTD dimerization interface, prevents HSP90 CTD dimerization, disrupts co-chaperone PPID binding to HSP90 CTD, and inhibits HSP90 chaperone function dependent on dimerization. VWK147 reduces protein levels of HSP90 client proteins ULK1, RIPK1, and CDK4 without inducing a heat shock response. VWK147 induces cell death, including apoptosis, in Cisplatin (HY-17394)-sensitive and -resistant urothelial carcinoma cells. VWK147 induces LC3-II accumulation, inhibits autophagosome-lysosome fusion to block canonical autophagy, and induces non-canonical LC3 lipidation independent of ULK1 and PIK3C3 complexes. VWK147 can be used for the research of urothelial carcinoma.
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- 화학식: C32H38N10O7
- 분자량:674.71
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보관:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- 순도&문서
- References
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Help & FAQs
Biological Activity
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HSP90 |
ULK1 |
CDK4 |
RIPK1 |
VWK147 inhibits the interaction between HSP90β CTD and PPID in a TR-FRET assay[1].
VWK147 (10 μM; 3 h) does not bind to the HSP90 NTD in a fluorescence polarization assay[1].
VWK147 (25-100 μM; 1 h) inhibits HSP90 chaperone function in a cell-free luciferase refolding assay[1].
VWK147 (2-50 μM; 1 h) reduces HSP90α CTD dimers in a BS3 crosslinker assay[1].
VWK147 (1-10 μM; 6 h) destabilizes HSP90 client proteins ULK1, RIPK1, and CDK4 in Cisplatin-sensitive T24 and Cisplatin-resistant T24-CR urothelial carcinoma cells[1].
VWK147 (0.1-100 μM; 72 h) reduces cell viability in Cisplatin-sensitive (253J, T24) and -resistant (253J-CR, T24-CR) urothelial carcinoma cells with IC50 values of ~3-5 μM after 72 h[1].
VWK147 (10 μM; 0-24 h) induces cell death with both apoptotic and necrotic properties in T24 and T24-CR urothelial carcinoma cells over 24 h[1].
VWK147 (5 μM; 24 h) induced cell death in 253J, 253J-CR, T24, and T24-CR urothelial carcinoma cells is partially caspase-dependent[1].
VWK147 (1-10 μM; 6 h) induces concentration-dependent PARP1 cleavage in T24 and T24-CR urothelial carcinoma cells[1].
VWK147 (5 μM; 1-24 h) induces time-dependent PARP1 cleavage in T24 and T24-CR urothelial carcinoma cells over 24 h[1].
VWK147 (5 μM; 0-24 h) induces caspase-3 activation in Cisplatin-sensitive (253J, T24) and -resistant (253J-CR, T24-CR) urothelial carcinoma cells over 24 h[1].
VWK147 (5 μM; 6 h) inhibits autophagic flux in T24 and T24-CR urothelial carcinoma cells, as shown by LC3-II accumulation[1].
VWK147 (5 μM; 4 h) inhibits autophagosome-lysosome fusion in T24 and T24-CR urothelial carcinoma cells stably expressing mRFP-EGFP-rLC3[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Cisplatin-sensitive (T24) and -resistant (T24-CR) urothelial carcinoma cells
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Concentration:1 μM, 3 μM, 5 μM, 10 μM
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Incubation Time:6 h
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Result:Reduced levels of HSP90 client proteins ULK1, RIPK1, and CDK4 in both T24 and T24-CR cells.\nDid not increase levels of HSP27, HSP40, or HSP70.
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Cell Line:Cisplatin-sensitive (253J, T24) and -resistant (253J-CR, T24-CR) urothelial carcinoma cells
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Concentration:0.1-100 μM
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Incubation Time:72 h
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Result:Reduced cell viability in all four cell lines with IC50 values of ~3-5 μM for 253J, ~3-5 μM for 253J-CR, ~3-5 μM for T24, and ~3-5 μM for T24-CR.
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Cell Line:253J, 253J-CR, T24, and T24-CR urothelial carcinoma cells
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Concentration:5 μM (with 20 μM Q-VD-OPh (HY-12305) as co-treatment)
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Incubation Time:24 h
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Result:Had its mediated cell viability reduction partially reduced by Q-VD-OPh but not abolished, indicating partial pro-apoptotic effects.
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Cell Line:T24 and T24-CR urothelial carcinoma cells
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Concentration:1-10 μM
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Incubation Time:6 h
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Result:Increased cleaved PARP1 levels in a concentration-dependent manner in both cell lines.
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Cell Line:T24 and T24-CR urothelial carcinoma cells
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Concentration:5 μM
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Incubation Time:1-24 h
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Result:Induced time-dependent PARP1 cleavage, with increased cleavage over 24 h.
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Cell Line:T24 and T24-CR urothelial carcinoma cells
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Concentration:5 μM (with 20 nM bafilomycin A1 as co-treatment)
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Incubation Time:6 h
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Result:Increased LC3-II levels with mono-treatment, but combination with Bafilomycin A1 did not further increase LC3-II levels, indicating inhibited autophagic flux; p62 levels were unaffected.
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Cell Line:T24 and T24-CR cells stably expressing mRFP-EGFP-rLC3
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Concentration:5 μM
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Incubation Time:4 h
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Result:Resulted in almost complete co-localization of GFP and RFP signals (yellow structures), indicating inhibited autophagosome-lysosome fusion (no red-only puncta).
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Cell Line:T24 and T24-CR urothelial carcinoma cells
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Concentration:5 μM (with 5 μM SAR405 as co-treatment)
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Incubation Time:4 h
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Result:Induced LC3-positive aggregates that were unaffected by SAR405, indicating PIK3C3-independent (non-canonical) LC3 lipidation.
Chemical Information
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분자량 674.71
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화학식 C32H38N10O7
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SMILES
CCC(N1C(C(NC(C2=NC=C(C(N2CC3=CC=C(C=C3)OC)=O)N)=O)=CN=C1C(NC4=CN=C(N(C4=O)CC(C)C)C(NC)=O)=O)=O)C
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Please store the product under the recommended conditions in the Certificate of Analysis.
순도&문서
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
VWK147 Related Classifications
HY-181062 Related Classifications
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