STING Degrader

AK59 is a STING degrader that works by leveraging HERC4, a hect domain E3 ligase. AK59 can be used in the study of autoimmune diseases and cancer.

PROTAC STING degrader-3 is a STING PROTAC degrader (DC₅₀: 0.62 μM). PROTAC STING degrader-3 induces STING degradation via the ubiquitin-proteasome pathway. PROTAC STING degrader-3 exerts anti-inflammatory effects by inhibiting STING/TBK1/NF-κB signaling. PROTAC STING degrader-3 has renal protective effects and can be used in the study of acute kidney injury (AKI).

KMR-206 is a PARP7 inhibitor with an IC₅₀ of 13.7 nM. KMR-206 relieves AHR-mediated transcriptional repression and enhances CYP1A1 expression in the presence of TCDD. KMR-206 induces the STING-dependent IFN-β signaling pathway and increases the levels of STAT1, pSTAT1 and nuclear PARP7 in cancer cells. KMR-206 reduces the viability of lung adenocarcinoma cells, enhances radiation-induced immunogenic signals, and induces the production of immunogenic signals in glioblastoma cancer stem cells. KMR-206 destabilizes FRA1 to increase IRF1 levels and promotes the IRF3-CBP/p300 interaction. KMR-206 can be used in studies related to lung adenocarcinoma and glioblastoma.

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.

PROTAC STING Degrader-2 is a STING PROTAC degrader with a DC₅₀ of 0.53 μM. PROTAC STING Degrader-2 reduces the phosphorylation levels of TBK1 and IRF3. PROTAC STING Degrader-2 decreases the mRNA expression levels of IFN-β, CXCL10 and TNF-α, and blocks luciferase secretion. PROTAC STING Degrader-2 can be used in the research of autoimmune diseases.

UNC8899 is a VHL-recruiting STING PROTAC degrader (DC₅₀: 0.0.924 μM). UNC8899 can be used for viral or bacterial infection research (Blue: VHL ligand, Black: linker; Pink: STING inhibitor).

STING Degrader-1 (compound 2), a molecular glue, is a potent STING degrader that covalently binds to STING and E3 ligase. STING Degrader-1 exhibits a "hook effect", that degrades 75% STING protein at 10 μM, and degrades ca. 30% STING protein at 30 μM.

UNC9036 is a STING PROTAC degrader with a DC₅₀ value of 227 nM. UNC9036 binds to and activates STING, recruits the VHL E3 ligase to target phosphorylated STING for ubiquitination and proteasomal degradation. UNC9036 inhibits downstream innate immune signaling events triggered by cytoplasmic DNA sensing, including IRF3 phosphorylation. UNC9036 reduces the antiviral response of cells infected with HSV-1. UNC9036 can be used in the research of renal cell carcinoma.

UNC8900 is a VHL recruiting STING PROTAC degrader (DC₅₀: 0.0.924 μM). UNC8900 can be used for research of viral or bacterial infection. (Blue: VHL ligand, black: linker; Pink: STING inhibitor).

Zp17 is a STING PROTAC degrader with a DC₅₀ of 956. Zp17 induces proteasome-dependent STING protein degradation and inhibits the activity of the STING signaling pathway. Zp17 alleviates renal function injury in a mouse model of acute kidney injury induced by Cisplatin (HY-17394). Zp17 exhibits STING-degrading activity in human monocytes and STING-inhibiting activity in mouse macrophage reporter cells. Zp17 can be used for research on inflammation and acute kidney injury.

STING Degrader-2 is an orally active STING degrader that promotes proteasome-independent degradation of STING. STING Degrader-2 inhibits cGAMP-induced STING activation, suppresses STING oligomerization, and inhibits phosphorylation of STING and interferon regulatory factor 3 (IRF3). STING Degrader-2 reduces serum IFN-β and CXCL-10 levels in a cGAMP-induced autoimmune disease mouse model. STING Degrader-2 can be used for the research of autoimmune diseases.

STING Degrader-3 is a PROTAC-like STING degrader with a DC₅₀ of 2.58 μM in THP-1 cells. STING Degrader-3 degrades STING protein via the lysosomal pathway. STING Degrader-3 functions as a non-degradative inhibitor in macrophages. STING Degrader-3 reduces the phosphorylation levels of TBK1 and IRF3, and downregulates the expression of IFN-β, CXCL10, IL-6, TNFα, IL-1β, ISG15 and ISG56. STING Degrader-3 exhibits renoprotective properties in a cisplatin-induced acute kidney injury model. STING Degrader-3 can be used in studies related to acute kidney injury. ((Pink: STING ligand (HY-168676); Blue: CRBN ligand (HY-126457); Black: linker (HY-W123015); CRBN ligand + linker: (HY-168677)).