GSI526
GSI526 is a IRAK4 PROTAC degrader (DC50=40.17 nM, Dmax=97%; THP-1) based on the VHL ubiquitin-proteasome system. GSI526 inhibits IRAK4-mediated NF-κB and MAPK inflammatory signaling pathways, and induces IRAK4 degradation in myeloid cells. GSI526 is applicable to inflammation-related research.
(Pink: IRAK4 ligand (HY-183800); Blue: VHL ligand (HY-112078); Black: linker).
Nur für Forschungszwecke. Wir verkaufen nicht an Patienten.
- Formel: C51H62N10O7S
- Molecular Weight:959.17
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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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VHL |
IRAK4 |
GSI526 (1-10000 nM; 24 h) induces dose-dependent degradation of IRAK4 in HEK293T cells with a DC50 of 50.89 nM and a Dmax greater than 80%[1].
GSI526 (0.01-30 μM; 24 h) exhibits no cytotoxicity in THP-1 cells at concentrations up to 30 μM following 24 h incubation[1].
GSI526 (0.01-30 μM; 48 h) exhibits no cytotoxicity in HEK293T cells at concentrations up to 30 μM following 48 h incubation[1].
GSI526 (1000 nM; 8 h) exhibits marked selectivity toward IRAK4 in THP-1 cells, with IRAK4 showing a statistically significant downregulation following 8 h treatment with 1000 nM GSI526[1].
GSI526 (1-5 μM; 1 h pretreatment, followed by 6 h LPS stimulation) inhibits LPS-induced activation of the IRAK4-NF-κB/MAPK signaling pathway in THP-1 cells via degradation of IRAK4[1].
GSI526 (0.3-3 μM; 1 h pretreatment, followed by 24 h LPS stimulation) dose-dependently inhibits LPS-induced expression of TNF-α and CXCL8 in THP-1 cells via suppression of the IRAK4-NF-κB/MAPK signaling pathway[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:THP-1 human monocytic leukemia cells
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Concentration:1-10000 nM (dose-response); 1 μM (time-course)
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Incubation Time:24 h (dose-response); 2-24 h (time-course)
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Result:Induced dose-dependent degradation of IRAK4 with a DC50 of 40.17 nM and a maximum degradation (Dmax) of 97%.
Resulted in detectable IRAK4 degradation within 2 h, with maximal degradation achieved by 8 h, and the degradative effect was sustained for up to 24 h.
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Cell Line:HEK293T human embryonic kidney cells
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Concentration:1-10000 nM
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Incubation Time:24 h
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Result:Induced dose-dependent degradation of IRAK4 with a DC50 of 50.89 nM and a Dmax greater than 80%.
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Cell Line:THP-1 human monocytic leukemia cells
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Concentration:0.01-30 μM
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Incubation Time:24 h
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Result:Did not induce cytotoxic cell death at concentrations up to 30 μM.
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Cell Line:HEK293T human embryonic kidney cells
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Concentration:0.01-30 μM
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Incubation Time:48 h
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Result:Did not induce cytotoxic cell death at concentrations up to 30 μM.
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Cell Line:THP-1 human monocytic leukemia cells
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Concentration:1-5 μM
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Incubation Time:1 h pretreatment, followed by 6 h LPS stimulation
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Result:Inhibited LPS-induced phosphorylation of JNK, p38, ERK, and p65 (NF-κB) in a concentration-dependent manner via IRAK4 degradation.
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Cell Line:THP-1 human monocytic leukemia cells
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Concentration:0.3-3 μM
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Incubation Time:1 h pretreatment, followed by 24 h LPS stimulation
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Result:Significantly inhibited LPS-induced secretion of pro-inflammatory cytokine TNF-α and chemokine CXCL8, with the inhibitory effect particularly evident at 1 and 3 μM.
Chemical Information
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Molecular Weight 959.17
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Formel C51H62N10O7S
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SMILES
O=C(C1=NC(C2=CC=NN2)=CC=C1)NC3=C(OC)C=C(N4CCC5(CN(C(CCCC(N[C@@H](C(C)(C)C)C(N6[C@H](C(N[C@@H](C)C7=CC=C(C8=C(C)N=CS8)C=C7)=O)C[C@@H](O)C6)=O)=O)=O)C5)CC4)C=C3
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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)