NUCC-0227579
NUCC-0227579 is a VHL-recruiting PROTAC degrader targeting CD73, with a DC50 of 0.32 μM. NUCC-0227579 synergistically mediates CD73 degradation through the ubiquitin-proteasome pathway and the lysosomal pathway. NUCC-0227579 inhibits the conversion of AMP to adenosine, abrogates adenosine-mediated immunosuppression, upregulates the activities of the NF-κB and NFAT pathways, and enhances the secretion, activation and proliferation levels of IFN-γ and TNF-α. NUCC-0227579 downregulates NAD+ synthesis in tumor cells, and inhibits the proliferation, migration and adhesion abilities of tumor cells under glutamine-deficient conditions. NUCC-0227579 significantly suppresses tumor growth in a humanized NSG mouse model of triple-negative breast cancer.
(Pink: CD73 Target protein ligand; Blue: VHL ligand (HY-125845); Black: linker (HY-128804)).
Nur für Forschungszwecke. Wir verkaufen nicht an Patienten.
- Formel: C53H58ClN11O9S
- Molecular Weight:1060.61
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Speicherung:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biologische Aktivität
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Chemical Information
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Biologische Aktivität
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NF-κB |
TNF-α |
NUCC-0227579 (compound C79) (0.01-30 μM; 6-24 h) efficiently degrades CD73 in human triple-negative breast cancer MDA-MB-468 cells, with a DC50 of 0.32 μM[1].
NUCC-0227579 (0.1-5 μM; 24 h) potently degrades CD73 in a dose-dependent manner in human triple-negative breast cancer MDA-MB-231 cells and human melanoma A375 cells[1].
NUCC-0227579 (10 μM; 24 h) exhibits CD73 nucleotidase inhibitory activity in human triple-negative breast cancer MDA-MB-468 cells comparable to that of conventional CD73 inhibitors; it degrades TGF-β-induced CD73 in human triple-negative breast cancer MDA-MB-468 cells[1].
NUCC-0227579 (10 μM; 1-24 h, 6 h exposure with post-washout assessment) induces rapid degradation of CD73 in human triple-negative breast cancer MDA-MB-468 cells, with maximal efficacy achieved at 24 h, and this degradation effect persists for at least 48 h after compound removal[1].
NUCC-0227579 increases the ubiquitination level of CD73 in human triple-negative breast cancer MDA-MB-231 cells and promotes its targeted degradation[1].
NUCC-0227579 binds directly to purified CD73 (KD = 920 nM) and VHL (KD = 270 nM) proteins, and forms a negatively cooperative ternary complex CD73-C79-VHL with an affinity of 1.4 μM[1].
NUCC-0227579 reduces intracellular NAD+ levels in human triple-negative breast cancer MDA-MB-231 cells in a CD73-dependent manner, through a mechanism of inhibiting CD73-mediated conversion of nicotinamide mononucleotide (NMN) to NR[1].
Pretreatment of human MDA-MB-231 triple-negative breast cancer (TNBC) cells with NUCC-0227579 enhances the NF-κB and NFAT signaling pathways in co-cultured Jurkat reporter T cells in a CD73-dependent manner[1].
NUCC-0227579 inhibits the proliferation of human triple-negative breast cancer MDA-MB-231 cells, and its therapeutic efficacy is enhanced under nutrient stress conditions[1].
NUCC-0227579 impairs the migratory capacity of human triple-negative breast cancer MDA-MB-231 cells, as well as the adhesive and migratory capacities of human pancreatic ductal adenocarcinoma PANC-1 cells, by inhibiting the non-nucleotidase function of CD73[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MDA-MB-231 human TNBC cells, A375 human melanoma cells
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Concentration:0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30 μM
0.1, 1.0, 5 μM -
Incubation Time:24 h
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Result:Degraded CD73 in human triple-negative breast cancer MDA-MB-468 cells, with a DC50 of 0.32 μM.
Induced dose-dependent CD73 degradation in both MDA-MB-231 and A375 cells, whereas the control compound NUCC-0228837 (C37) failed to induce degradation.
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Cell Line:MDA-MB-468 human TNBC cells
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Concentration:10 μM
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Incubation Time:1, 3, 6, 24 h; 6 h exposure with 0, 12, 24, 48, 72 h post-washout assessment
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Result:Induced CD73 degradation as early as 1 h after treatment, reaching maximal efficacy at approximately 24 h post-treatment.
Maintained decreased CD73 protein levels for at least 48 h after compound removal following a 6-h exposure.
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Cell Line:MDA-MB-231 human TNBC cells
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Concentration:5 μM
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Incubation Time:48 h
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Result:Impaired migration of MDA-MB-231 human TNBC cells by inhibiting non-nucleotidase functions of CD73.
NUCC-0227579 (10 mg/kg; i.p.; daily; 14 days) is evaluated for antitumor efficacy in a humanized NSG mouse model of MDA-MB-468 triple-negative breast cancer[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NSG mice (female, humanized with PBMC intravenous injection on day -3, +3, +7 post-tumor inoculation)[1]
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Dosage:10 mg/kg; 30 mg/kg
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Administration:i.p.; daily (10 mg/kg); twice weekly (30 mg/kg); 14 days
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Result:Significantly suppressed tumor growth and reduced tumor weight at study end point.
Significantly reduced CD73 protein levels on CD45- tumor cells compared to vehicle controls.
Increased IFN-γ and TNF-α production from intratumoral CD8+ T cells.
Chemical Information
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Molecular Weight 1060.61
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Formel C53H58ClN11O9S
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SMILES
O=C(N1)NC2=C1C=C(N3N=NC4=C3C=C(C5=CC=NN5CC6=CC=C(OCCOCCOCCOCC(N[C@@H](C(C)(C)C)C(N7C[C@H](O)C[C@H]7C(NCC8=CC=C(C9=C(C)N=CS9)C=C8)=O)=O)=O)C=C6)C=C4Cl)C=C2
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Please store the product under the recommended conditions in the Certificate of Analysis.
Reinheit & Dokumentation
Verweise
Calculators
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
NUCC-0227579 Related Classifications
HY-184969 Related Classifications
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- NUCC-0227579
- NUCC0227579
- NUCC 0227579
- PROTACs
- CD73
- NF-κB
- Nuclear Factor of activated T Cells (NFAT)
- IFNAR
- TNF Receptor
- CD8+ T cell
- NF-κB/NFAT signaling
- PANC-1 human PDAC cells
- proteolysis-targeting chimera
- MDA-MB-468 human TNBC cells
- VHL E3 ligase
- A375 human melanoma cells
- MDA-MB-231 human TNBC cells
- triple-negative breast cancer
- Inhibitor
- inhibitor
- inhibit