PROTAC 20S proteasome subunit β5 degrader 1
PROTAC 20S proteasome subunit β5 degrader 1 is a PROTAC degrader targeting the 20S proteasome subunit β5, with a DC50 of 0.11 μM. PROTAC 20S proteasome subunit β5 degrader 1 forms a ternary complex with the CRBN E3 ligase, induces ubiquitination of the 20S proteasome subunit β5, and promotes its degradation via the proteasomal pathway. PROTAC 20S proteasome subunit β5 degrader 1 disrupts cell cycle progression, promotes apoptosis, and inhibits cell proliferation and migration. PROTAC 20S proteasome subunit β5 degrader 1 exhibits significant proliferation-inhibitory activity against various tumor cells, suppresses tumor growth in in vivo xenograft models, and overcomes the resistance of multiple myeloma cells to Bortezomib (HY-10227). PROTAC 20S proteasome subunit β5 degrader 1 can be used in studies related to pharyngeal cancer and drug-resistant multiple myeloma.
(Pink: 20S proteasome subunit β5 ligand (HY-10227); Blue: Cereblon ligand (HY-103596); Black: linker (HY-169142)).
For research use only. We do not sell to patients.
- Formula: C54H67BN6O11
- Molecular Weight:986.95
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Biological Activity
PROTAC 20S proteasome subunit β5 degrader 1 (compound 12f) binds tightly to recombinant human 20S proteasome β5 subunit in SPR-based cell-free binding assays (KD = 1.00 μM), and binds moderately to recombinant human CRBN (KD = 28.3 μM). It induces the formation of a 20S proteasome subunit β5-compound-CRBN ternary complex in FaDu and KM3/BTZ cells, and this complex mediates the targeted degradation of 20S proteasome subunit β5[1].
PROTAC 20S proteasome subunit β5 degrader 1 (3 days) potently inhibits the proliferation of various human cancer cell lines, with the strongest activity against FaDu cells (IC50 = 0.16 μM); meanwhile, due to its low cytotoxicity against normal HFF-1 and HL7702 cells, it exhibits a favorable therapeutic window against both FaDu cells and Bortezomib (HY-10227)-resistant KM3/BTZ cells[1].
PROTAC 20S proteasome subunit β5 degrader 1 (0.05-5 μM; 24 h) efficiently and selectively degrades the 20S proteasome subunit β5 in FaDu cells (DC50 = 0.11 μM, Dmax = 87%) and KM3/BTZ cells, while inducing dose-dependent and time-dependent accumulation of ubiquitinated proteins in both cell lines[1].
PROTAC 20S proteasome subunit β5 degrader 1 (0.1-1 μM; 24 h) dose-dependently inhibits the migration of human pharyngeal squamous cell carcinoma FaDu cells in wound healing assays[1].
PROTAC 20S proteasome subunit β5 degrader 1 (0.01-0.5 μM; 10 days) dose-dependently inhibits colony formation of FaDu human pharyngeal squamous cell carcinoma cells[1].
PROTAC 20S proteasome subunit β5 degrader 1 (0.01-10 μM; 24 h) induces apoptosis in a dose-dependent manner in human pharyngeal squamous cell carcinoma FaDu cells and Bortezomib-resistant multiple myeloma KM3/BTZ cells; it also alters cell cycle progression in a dose-dependent manner, arresting cells at the G2/M phase[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Human pharyngeal squamous cell carcinoma FaDu cells, Bortezomib-resistant multiple myeloma KM3/BTZ cells
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Concentration:0.05, 0.1, 0.5, 1, 5 μM (24 h incubation)
0.5 μM (time-course incubation) -
Incubation Time:24 h (dose-dependent
0, 2, 4, 8, 16, 24 h (time-dependent) -
Result:Induced dose-dependent degradation of 20S proteasome subunit β5 in FaDu cells (DC50 = 0.11 μM, Dmax = 87%) and dose- and time-dependent accumulation of ubiquitinated proteins at a minimum effective concentration of 0.05 μM and earliest action time of 2 h.
Induced dose- and time-dependent β5 degradation and ubiquitinated protein upregulation in KM3/BTZ cells within the concentration range of 0.05-5 μM and treatment duration of 2-24 h.
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Cell Line:Human pharyngeal squamous cell carcinoma FaDu cells
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Concentration:0.1, 0.5, 1 μM
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Incubation Time:24 h
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Result:Significantly reduced FaDu cell migration in a dose-dependent manner compared to DMSO-treated control cells.
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Cell Line:Human pharyngeal squamous cell carcinoma FaDu cells
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Concentration:0.01, 0.5 μM
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Incubation Time:10 days, media refreshed every 2 days
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Result:Inhibited FaDu cell colony formation in a dose-dependent manner compared to DMSO-treated control cells.
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Cell Line:Human pharyngeal squamous cell carcinoma FaDu cells, Bortezomib-resistant multiple myeloma KM3/BTZ cells
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Concentration:0.01, 0.1, 1, 10 μM
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Incubation Time:24 h
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Result:Increased the percentage of apoptotic cells in FaDu cells in a dose-dependent manner, with effects comparable to Bortezomib.
Increased apoptotic cell populations in KM3/BTZ cells in a dose-dependent manner.
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Cell Line:Human pharyngeal squamous cell carcinoma FaDu cells, Bortezomib-resistant multiple myeloma KM3/BTZ cells
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Concentration:0.01, 0.1, 1, 10 μM
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Incubation Time:24 h
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Result:Reduced the G1 population and increased the G2/M population in FaDu cells in a dose-dependent manner, with effects comparable to Bortezomib.
Induced dose-dependent G2/M cell cycle arrest in KM3/BTZ cells.
PROTAC 20S proteasome subunit β5 degrader 1 (administered via intraperitoneal injection once weekly at a dose of 2-4 mg/kg) induces 55.4% tumor growth inhibition in Bortezomib-resistant KM3/BTZ multiple myeloma xenografts[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c nude mice (5-week-old, 4 x 106 cells in 200 μL PBS)[1]
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Dosage:2 mg/kg
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Administration:i.p.; once weekly; 3 weeks
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Result:Achieved a tumor growth inhibition (TGI) rate of 51.1%.
Reduced tumor volume and weight significantly compared to the control group.
Decreased 20S proteasome subunit β5-positive cells, increased ubiquitin-positive cells, and enhanced tumor necrosis relative to controls.
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Animal Model:BALB/c nude mice (5-week-old, 2 x 107 cells in PBS+Matrigel (1:1, 200 μL))[1]
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Dosage:2 mg/kg; 4 mg/kg
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Administration:i.p.; once weekly
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Result:Achieved a 55.4% tumor growth inhibition (TGI) rate at the 4 mg/kg dose.
Reduced tumor volume and weight significantly at both 2 mg/kg and 4 mg/kg doses compared to the control group.
Outperformed the Bortezomib + Thalidomide (HY-14658) control treatment (18.5% TGI) at both doses.
Reduced 20S proteasome subunit β5-positive cells, increased ubiquitin-positive cells, and enhanced tumor necrosis relative to controls.
Chemical Information
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Molecular Weight 986.95
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Formula C54H67BN6O11
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SMILES
O=C1CCC(C(N1)=O)N2C(C3=C(C(OCC(NCCCCCCCNC(C4=CC=C(C=C4)C(N[C@@H](CC5=CC=CC=C5)C(N[C@H](B6O[C@@]7(C)[C@@H](C[C@H]8CC7O6)C8(C)C)CC(C)C)=O)=O)=O)=O)=CC=C3)C2=O)=O
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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
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
PROTAC 20S proteasome subunit β5 degrader 1 Related Classifications
HY-169134 Related Classifications
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