WRN degrader-1
WRN degrader-1 is a selective WRN degrader derived from H3B-219. WRN degrader-1 contains a proximity-activated sulfonamide pyrimidine warhead and an adamantane hydrophobic tag, covalently modifies WRN helicase, and potently degrades WRN via the ubiquitin-proteasome pathway. WRN degrader-1 degrades WRN in MSI-H and MSS cells. WRN degrader-1 induces apoptosis, cell cycle arrest, and DNA damage, and exerts WRN-dependent antiproliferative activity. WRN degrader-1 can be used in cancer-related research.
For research use only. We do not sell to patients.
- CAS No.: 3095277-20-3
- Formula: C37H44F3N5O5S
- Molecular Weight:727.84
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
Description
WRN degrader-1 is a selective WRN degrader derived from H3B-219. WRN degrader-1 contains a proximity-activated sulfonamide pyrimidine warhead and an adamantane hydrophobic tag, covalently modifies WRN helicase, and potently degrades WRN via the ubiquitin-proteasome pathway. WRN degrader-1 degrades WRN in MSI-H and MSS cells. WRN degrader-1 induces apoptosis, cell cycle arrest, and DNA damage, and exerts WRN-dependent antiproliferative activity. WRN degrader-1 can be used in cancer-related research[1].
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HCT-116 | DC50 |
1.7 μM
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WRN degradation in human HCT-116 cells after 24 hrs exposure by Western blot.
WRN degradation in human HCT-116 cells after 24 hrs exposure by Western blot.
|
40921117 |
| SW48 | DC50 |
3.0 μM
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WRN degradation in human SW-48 cells after 24 hrs exposure by Western blot.
WRN degradation in human SW-48 cells after 24 hrs exposure by Western blot.
|
40921117 |
| SW480 | DC50 |
5.9 μM
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WRN degradation in human SW-480 cells after 24 hrs exposure by Western blot.
WRN degradation in human SW-480 cells after 24 hrs exposure by Western blot.
|
40921117 |
| HCT-116 | IC50 |
2.7 μM
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Antiproliferative activity against human HCT-116 cells assessed as viability reduction after 5 days exposure by CCK8 assay.
Antiproliferative activity against human HCT-116 cells assessed as viability reduction after 5 days exposure by CCK8 assay.
|
40921117 |
| SW48 | IC50 |
0.1 μM
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Antiproliferative activity against human SW-48 cells assessed as viability reduction after 5 days exposure by CCK8 assay.
Antiproliferative activity against human SW-48 cells assessed as viability reduction after 5 days exposure by CCK8 assay.
|
40921117 |
In Vitro
Anti-cancerApoptosisCell Cycle RegulationProtein/Amino Acid MetabolismOthers
Anti-cancer
WRN degrader-1 (5 days) selectively inhibits MSI-H cell growth, with IC50 values of 2.7 µM and 0.1 µM in HCT-116 and SW-48, respectively, while having no effect on MSS SW-480 cells[1].
WRN degrader-1 (10 µM; 0-3 days) exhibits WRN-dependent antiproliferative activity in HCT-116 cells[1].
WRN degrader-1 (5-20 µM; 0-6 days) completely inhibits HCT-116 cell growth at 10 and 20 µM within 6 days[1].
WRN degrader-1 (1.25-20 µM; 14 days) inhibits long-term colony formation of HCT-116[1].
WRN degrader-1 (10 µM; 0-48 h) inhibits HCT-116 migration at 10 µM[1].
WRN degrader-1 (10 µM; 16 h) induces extensive transcriptional reprogramming in HCT-116 cells without altering WRN mRNA levels[1].
WRN degrader-1 (10 µM; 0-3 days) exhibits WRN-dependent antiproliferative activity in HCT-116 cells[1].
WRN degrader-1 (5-20 µM; 0-6 days) completely inhibits HCT-116 cell growth at 10 and 20 µM within 6 days[1].
WRN degrader-1 (1.25-20 µM; 14 days) inhibits long-term colony formation of HCT-116[1].
WRN degrader-1 (10 µM; 0-48 h) inhibits HCT-116 migration at 10 µM[1].
WRN degrader-1 (10 µM; 16 h) induces extensive transcriptional reprogramming in HCT-116 cells without altering WRN mRNA levels[1].
Anti-cancer
Apoptosis
Cell Cycle Regulation
Protein/Amino Acid Metabolism
WRN degrader-1 (1-10 µM; 24 h) degrades WRN in HCT-116 cells, with a degradation rate of 95% at 10 µM[1].
WRN degrader-1 (0.01-50 µM; 24 h) is a potent, phenotype-independent WRN degrader with the strongest activity in HCT-116 cells, with a DC50 of 1.7 µM[1].
WRN degrader-1 (0.1-25 µM; 24 h) selectively degrades WRN in HCT-116 cells, and no loss of other RecQ family proteins or POLθ is detected at concentrations up to 25 µM[1].
WRN degrader-1 (10 µM; 0-24 h) accelerates the turnover of WRN in HCT-116 cells[1].
WRN degrader-1 induces proteasome-dependent WRN degradation in HCT-116 cells, and this degradation is enhanced by HSP90 inhibition; it also promotes WRN ubiquitination in HCT-116 cells[1].
WRN degrader-1 (0.01-50 µM; 24 h) is a potent, phenotype-independent WRN degrader with the strongest activity in HCT-116 cells, with a DC50 of 1.7 µM[1].
WRN degrader-1 (0.1-25 µM; 24 h) selectively degrades WRN in HCT-116 cells, and no loss of other RecQ family proteins or POLθ is detected at concentrations up to 25 µM[1].
WRN degrader-1 (10 µM; 0-24 h) accelerates the turnover of WRN in HCT-116 cells[1].
WRN degrader-1 induces proteasome-dependent WRN degradation in HCT-116 cells, and this degradation is enhanced by HSP90 inhibition; it also promotes WRN ubiquitination in HCT-116 cells[1].
Others
WRN degrader-1 (compound 14C) covalently labels the WRN helicase domain, reaching 78% monoadduct formation after 48 h at 4 °C[1].
WRN degrader-1 (10 µM; 0-36 h) directly binds and thermally stabilizes WRN in HCT-116 cells, and induces rapid and sustained WRN degradation, with persistent degradation after removal[1].
WRN degrader-1 (10 µM; 0-36 h) directly binds and thermally stabilizes WRN in HCT-116 cells, and induces rapid and sustained WRN degradation, with persistent degradation after removal[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Western Blot Analysis[1]
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Cell Line:HCT-116 (MSI-H) cells
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Concentration:10 and 1 µM
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Incubation Time:24 h
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Result:Degraded WRN in HCT-116 cells, with 95% degradation at 10 µM.
Western Blot Analysis[1]
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Cell Line:HCT-116, SW-48 (MSI-H), and SW-480 (MSS) cells
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Concentration:0.01, 0.05, 0.1, 0.5, 1, 5, 10, 25, 50 µM (HCT-116)
0.1, 0.5, 1, 2.5, 5, 10, 25 µM (SW-48)
0.1, 0.5, 1, 5, 10, 25, 50 µM (SW-480) -
Incubation Time:24 h
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Result:Yielded DC50 of 1.7 µM and Dmax of 98.0 % in HCT‑116 cells, attained DC50 of 3.0 µM and Dmax of 98.0 % in SW‑48 cells, and achieved DC50 of 5.9 µM with Dmax of 99.0 % in SW‑480 cells.
Western Blot Analysis[1]
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Cell Line:HCT-116 cells
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Concentration:0.1, 1, 5, 10, 25 µM
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Incubation Time:24 h
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Result:Exhibited dose‑dependent WRN degradation, and exerted negligible influences on RECQ1, RECQ4, RECQ5, POLθ, and BLM even at 25 µM.
Western Blot Analysis[1]
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Cell Line:HCT-116 cells
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Concentration:10 µM
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Incubation Time:0, 2, 4, 6, 8, 10, 12, 24, 36 h
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Result:Achieved rapid WRN depletion by 10 h and maintained sustained protein depletion up to 36 h.
Western Blot Analysis[1]
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Cell Line:HCT-116 cells
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Concentration:10 µM
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Incubation Time:10 h exposure; washout at 0, 4, 8, 12, 24, 36 h
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Result:Retained persistent WRN degradation for up to 36 h following compound washout.
Western Blot Analysis[1]
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Cell Line:HCT-116 cells
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Concentration:10 µM; cycloheximide 10 µM
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Incubation Time:0, 2, 4, 6, 12, 24 h
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Result:Produced markedly‑accelerated WRN degradation and shortened WRN protein half‑life.
Cell Proliferation Assay[1]
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Cell Line:HCT-116 cells
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Concentration:5, 10, 20 µM
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Incubation Time:0, 1, 2, 3, 4, 5, 6 days
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Result:Suppressed HCT-116 cell growth at 10 and 20 µM over 6 days.
Cell Proliferation Assay[1]
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Cell Line:HCT-116 cells
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Concentration:1.25, 2.5, 5, 10, 20 µM
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Incubation Time:14 days
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Result:Suppressed long-term HCT-116 colony formation over 14 days.
Cell Migration Assay [1]
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Cell Line:HCT-116 cells
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Concentration:10 µM
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Incubation Time:0, 24, 48 h
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Result:Inhibited HCT-116 migration at 10 µM.
Apoptosis Analysis[1]
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Cell Line:HCT-116 cells
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Concentration:1, 5, 10 µM
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Incubation Time:24 h
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Result:Induced apoptosis in HCT-116 cells at 1-10 µM.
Cell Cycle Analysis[1]
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Cell Line:HCT-116 cells
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Concentration:1, 5, 10 µM
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Incubation Time:24 h
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Result:Induced G2/M cell-cycle arrest in HCT-116 cells at 1-10 µM.
Immunofluorescence[1]
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Cell Line:HCT-116 cells
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Concentration:1, 5, 10 µM
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Incubation Time:24 h
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Result:Dose-dependent increases in γ-H2AX foci were observed.
Related Protocols :
- Detection of Apoptosis
- TUNEL staining for apoptotic DNA fragmentation
- Flow cytometric DNA-content cell-cycle staining
- Annexin V plus membrane-impermeant dye apoptosis staining
- BrdU Incorporation Assay
- Apoptosis Solutions
- Protocol for Cell Cycle
- Genotoxicity/Mutagenicity Study
- Cell Viability Determination by MTT Colorimetric Assay
Chemical Information
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CAS No. 3095277-20-3
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Molecular Weight 727.84
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Formula C37H44F3N5O5S
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SMILES
O=C(NCCCCCOC1=CC=C(C2=NC(S(=O)(NCC(NC3=CC=C(C)C=C3)=O)=O)=NC(C(F)(F)F)=C2)C=C1)CC45C[C@H](C6)C[C@@H](C5)C[C@H]6C4
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
Select Batch:
Purity:
99.98%
Assay:
99.98%
ee.:
99.98%
References
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WRN degrader-1 Related Classifications
HY-178474 Related Classifications
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