PROTAC STING degrader-4

Cat. No.: HY-176180: Data Sheet Handling Instructions
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PROTAC STING degrader-4 is a nitro-free covalent STING PROTAC degrader with a DC₅₀ of 3.23 μM. PROTAC STING degrader-4 effectively inhibits STING as well as its downstream signaling, such as p-TBK1 and p-NF-κB (p-P65), and immune-inflammatory cytokines. PROTAC STING degrader-4 mitigates kidney and blood inflammation in Cisplatin (HY-17394)-induced acute kidney injury (AKI) mice model. Pink: STING ligand (HY-176183); Blue: CRBN ligase ligand (HY-103596); Black: linker (HY-176182); CRBN ligase ligand + linker: HY-176181

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PROTAC STING degrader-4 Chemical Structure

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IKK-α IKK-β IKK IKKε TBK1

Biological Activity
Purity & Documentation
References
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Description

PROTAC STING degrader-4 is a nitro-free covalent STING PROTAC degrader with a DC₅₀ of 3.23 μM. PROTAC STING degrader-4 effectively inhibits STING as well as its downstream signaling, such as p-TBK1 and p-NF-κB (p-P65), and immune-inflammatory cytokines. PROTAC STING degrader-4 mitigates kidney and blood inflammation in Cisplatin (HY-17394)-induced acute kidney injury (AKI) mice model^[1]. Pink: STING ligand (HY-176183); Blue: CRBN ligase ligand (HY-103596); Black: linker (HY-176182); CRBN ligase ligand + linker: HY-176181

IC₅₀ & Target^[1]

NF-κB

TBK1

In Vitro

PROTAC STING degrader-4 (Compound 2h) (0.6-40 μM, 2-72 h) dose- and time- dependently degrades STING for 72 h, with a DC₅₀ of 3.23 μM (24 h) in THP-1 dual cells^[1].
PROTAC STING degrader-4 (10 μM, 48 h) induces the degradation of STING via the proteasome pathway^[1].
PROTAC STING degrader-4 (0.3-20 μM, 16 h) dose-dependently reduced protein levels of p-TBK1 and p-NF-κB (p-P65), suppressing the STING downstream signaling cascade beyond direct degradation of STING in THP1-Dual cells^[1].
PROTAC STING degrader-4 (0.6-20 μM, 2 h) significantly and dose-dependently decreases the production of IFN-β and CXCL10 and inhibits IFNB1, CXCL10 and ISG15 mRNA expression in THP1-Dual cells induced by MSA-2 (HY-136927)^[1].
PROTAC STING degrader-4 (0.03-30 μM, 24-48 h) exhibits a no or weak cytotoxicity in THP1-Dual and RAW-Lucia cells (below 20 μM) and in human and mouse normal cells (below 30 μM)^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Western Blot Analysis^[1]

Cell Line:	THP-1 dual cells
Concentration:	0.6, 1.2, 2.5, 5, 10, 20, 40 μM
Incubation Time:	2, 4, 8, 12, 24, 48, 72 h
Result:	Dose-dependently degraded STING with a DC₅₀ of 3.23 μM (24 h) in THP-1 dual cells. Continuously reduced the expression level of STING in THP1-dual cells for 72 h in THP-1 dual cells. Induced potent degradation of STING, and this degradation effect was not inhibited by lysosome inhibitor BAF (Bafilomycin A1) (HY-100558) but was reversed by proteasome inhibitor MG132 (HY-13259) Induced the degradation of STING via the proteasome pathway rather than its warhead molecule or E3 ligase ligand, BAF (a lysosome inhibitor) and MG132 (a proteasome inhibitor).

Western Blot Analysis^[1]

Cell Line:	THP-1 dual cells
Concentration:	0.3, 0.6, 1.25, 2.5, 5, 10, 20 μM
Incubation Time:	2 h following MSA-2 (10 μM) for 16 h
Result:	Dose-dependently reduced protein levels of p-TBK1 and p-NF-κB (p-p65), suppressing the STING downstream signaling cascade beyond direct degradation of STING.

Real Time qPCR^[1]

Cell Line:	THP-1 dual cells
Concentration:	0.6, 1.25, 2.5, 5, 10, 20 μM
Incubation Time:	2 h following MSA-2 (10 μM) for 24 h
Result:	Significantly and dose-dependently inhibited IFNB1, CXCL10 and ISG15 mRNA expression in THP1-Dual cells.

Cell Viability Assay^[1]

Cell Line:	THP1-Dual, RAW-Lucia cells, human normal cell lines (HEK293T and WI38VA-13) and mouse normal cell lines (HT22 and MEF).
Concentration:	0.03, 0.07, 0.15, 0.31, 0.62, 1.25, 2.5, 5, 10, 20 μM (THP1-Dual and RAW-Lucia cells), 1.1, 3.3, 10, 30 μM (four human and mouse normal cell lines)
Incubation Time:	24, 48 h
Result:	Did not exhibit significant inhibition of cellular viability below 20 μM in THP1-Dual and RAW-Lucia cells. Exhibited no or weak cytotoxicity against four human and mouse cell lines at concentrations below 30 μM.

In Vivo

PROTAC STING degrader-4 (Compound 2h) (30 mg/kg, i.p., daily for 3 days) significantly relieves renal inflammation by degrading STING and downstream signaling pathways, such as p-IRF3 in Cisplatin-induced AKI mice model^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	Male C57BL/6 mice (8 weeks old) were given Cisplatin administration (15 mg/kg) 1 h after PROTAC STING degrader-4 to induce AKI mice model^[1].
Dosage:	30 mg/kg
Administration:	i.p., daily for 3  days and then collected blood and kidney samples after cisplatin induction¹.
Result:	Potently mitigated ischemic symptoms of kidneys. Significantly reduced the protein level of STING and p-IRF3 in kidney tissues. Effectively reduced the mRNA levels of Tnfα, Isg15 and Cxcl10. Effectively suppressed the production of CXCL10, IFN-β, IL-6 in plasma.

Molecular Weight

837.70

Formula

C₃₉H₄₂Cl₂N₈O₉

SMILES

ClC(C=C(C=N1)NC(NC2=CNC3=CC=C(C=C32)Cl)=O)=C1N(CC4)CCN4CCOCCOCCOCCOC5=C6C(N(C(C6=CC=C5)=O)C7CCC(NC7=O)=O)=O

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Purity & Documentation

Handling Instructions (2659 KB)

References

[1]. An Y, et al. Discovery of indole derivatives as STING degraders. Eur J Med Chem. 2025 May 12; 294:117747. [Content Brief]