STAT1 Inhibitor

Deucravacitinib (BMS-986165) is an orally active allosteric inhibitor of tyrosine kinase 2 (TYK2), with an IC₅₀ of 0.2 nM and a K_i of 0.02 nM against the JH2 domain of TYK2, and it exhibits selectivity over other JAK subtypes and most of the kinome. Deucravacitinib blocks IL-23, IL-12, p-STAT1/3 and Type I IFN signaling, and inhibits Th17/Th1-mediated psoriasis inflammation. Deucravacitinib can be used in research related to moderate-to-severe plaque psoriasis, inflammatory bowel disease and systemic lupus erythematosus.

C188-9 (TTI-101) is a STAT3 inhibitor with a K_d value of 4.7 nM. C188-9 targets the SH2 domain of STAT3, blocks the processes of STAT3 ligand binding, receptor recruitment, homodimerization and phosphorylation, and regulates STAT3-mediated genes associated with tumorigenesis and radioresistance. C188-9 regulates STAT1-mediated genes related to radioresistance and reduces the activation level of STAT1. C188-9 downregulates the expression of DNMT1, enhances DAC-induced demethylation and re-expression of RASSF1A, and simultaneously potentiates the anti-tumor effect of DAC on pancreatic cancer cells. C188-9 inhibits both anchorage-dependent and anchorage-independent growth of cancer cells, induces Apoptosis, blocks the growth of tumor xenografts, and suppresses muscle atrophy. C188-9 maintains muscle mass, increases body weight and improves grip strength in tumor-bearing mice. C188-9 can be used in research related to head and neck squamous cell carcinoma, pancreatic cancer, sepsis-related skeletal muscle wasting, non-small cell lung cancer, acute myeloid leukemia and cancer cachexia.

Anti-Mouse NK1.1 Antibody (PK136) is an anti-mouse NK1.1 IgG2a monoclonal antibody. Anti-Mouse NK1.1 Antibody (PK136) can deplete natural killer (NK) cells. Anti-Mouse NK1.1 Antibody (PK136) inhibits the JAK-STAT and NF-κB signaling pathways. Anti-Mouse NK1.1 Antibody (PK136) can be used for research on inflammation conditions such as non-alcoholic steatohepatitis (NASH).

Erasin is a potent Erlotinib (HY-50896)-resistance antagonizing STAT3 inhibitor with IC₅₀s of 9.7 and 24 μM against STAT3 and STAT1, respectively. Erasin induces cancer cells apoptosis.

ZDZ-553 is an orally active STAT1 inhibitor with an IC₅₀ value of 0.87 μM. ZDZ-553 modulates STAT1 signaling to affect downstream lipid metabolism and inflammatory pathways. ZDZ-553 attenuates hepatic steatosis in NASH mouse models. ZDZ-553 reduces inflammatory responses in NASH mouse models. ZDZ-553 can be used for the research of nonalcoholic steatohepatitis.

IFN-α Receptor Recognition Peptide 1 acetate (IRRP1 acetate) is an amino acid synthetic peptide and also a regulator of IFN-α Receptor. IFN-α Receptor Recognition Peptide 1 acetate binds to IFNAR2, enhances the binding capacity of IFN-α receptor, and slightly increases the IFN-α-induced growth inhibitory activity. IFN-α Receptor Recognition Peptide 1 acetate inhibits IFN-α-induced STAT1 phosphorylation and STAT-DNA binding by blocking the activation of IFNAR by IFN-α. IFN-α Receptor Recognition Peptide 1 acetate increases the occupancy of IFN-α on cell surface receptors, enhances the phosphorylation activation of ISGF3, and elevates IFN-α-induced antiviral activity. IFN-α Receptor Recognition Peptide 1 acetate can be used in studies related to encephalomyocarditis virus infection.

STAT4-IN-1 is an inhibitor of STAT4 with a K_i of 0.35 μM. STAT4-IN-1 is expected to be used in the research of autoimmune diseases, including inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, and diabetes.

STAT1/3-IN-1 is a potent STAT1/3 inhibitor with potent anti-inflammatory effect. STAT1/3-IN-1 inhibits phosphorylation and nuclear translocation of STAT1/3 to modulate microglial inflammation, reduces LPS (HY-D1056)-induced pro-inflammatory cytokines (NO, IL-1β, IL-6, and TNF-α) and inflammatory mediators (iNOS, COX-2). STAT1/3-IN-1 exhibits low toxicity in mice. STAT1/3-IN-1 can be used for the research of neuroinflammation.

Sm4 is a selective and orally active SOX18 inhibitor. Sm4 inhibits SOX18-DNA binding (IC₅₀ = 97.5 μM); Sm4 disrupts the SOX18-RBPJ protein-protein interaction (IC₅₀ = 42.3 μM). Sm4 blocks SOX18 DNA binding, disrupts multiple SOX18 protein-protein interactions with RBPJ, DDX1, DDX17, ILF3, SOX7 and STAT1, modulates SOX18 chromatin binding dynamics. Sm4 exerts anti‑angiogenic and anti‑lymphangiogenic effects, reduces tumor vascular density, triggers vascular defects in zebrafish, prolongs survival in mouse metastatic cancer models. Sm4 can be used for the research of breast cancer.

Anthraquinone-2-carboxylic acid is an orally active anthraquinone compound and Antibacterial agent. Anthraquinone-2-carboxylic acid can be isolated from Bajitian. Anthraquinone-2-carboxylic acid inhibits the activation of DPP-IV, COX-2, NF-κB and AP-1. Anthraquinone-2-carboxylic acid blocks IAV-induced activation of the RIG-I/STAT1 pathway, alleviates IAV-mediated weight loss, and protects against lethal IAV infection. Anthraquinone-2-carboxylic acid inhibits the growth of various Staphylococcus strains. It possesses potent anti-inflammatory, immunomodulatory, analgesic and antibacterial activities.\n

LL-K8-22 is a potent, selective and durable PROTAC CDK8-cyclin C dual degrader, with DC₅₀ values of 2.52 and 2.64 μM, respectively. LL-K8-22 also suppresses STAT1 Ser 727 phosphorylation. LL-K8-22 inhibits E2F- and MYC-driven carcinogenic transcriptional programs. LL-K8-22 can be used for triplenegative breast cancer (TNBC) research.

PROTAC TYK2 degrader-1 is a TYK2 PROTAC degrader with a D_max ≥ 60%. PROTAC TYK2 degrader-1 reduces the phosphorylation levels of IFNα-induced STAT1 (Tyr701) and STAT3 (Tyr705) in immune cells. PROTAC TYK2 degrader-1 can be used in research on cancer, inflammatory diseases, etc.

Pheophytin a is a multi-target inhibitor, anticancer agent, antioxidant and antiviral agent. Pheophytin a directly binds to and inhibits HCV-NS3/4A protease (IC₅₀=0.89 μM) to block viral replication. Pheophytin a also scavenges free radicals, reduces ferric ions, and exhibits cytotoxic activity against breast cancer cells. Pheophytin a effectively inhibits LPS-induced production of nitric oxide, prostaglandin E2, NOS2 and COX-2, as well as various pro-inflammatory cytokines, by downregulating the transcription levels of inflammatory mediators and blocking the ERK1/2 and STAT-1 pathways. In a low nerve growth factor environment, Pheophytin a also enhances ERK1/2 phosphorylation and synergistically promotes neurite outgrowth through MAPK pathway. Pheophytin a can be used to investigate the pathogenic mechanisms of diseases including chronic hepatitis C, sepsis, breast cancer and Alzheimer's disease.

QL-1200186 is a selective, orally active, allosteric inhibitor targeting the tyrosine kinase TYK2 pseudokinase domain JH2 (IC₅₀=0.06 nM, TYK2 JH2), with 164-fold selectivity over TYK1 JH2 (IC₅₀=9.85 nM，TYK1 JH2). QL-1200186 first stabilizes the TYK2 JH2 conformation, inhibits the activity of the JH1 catalytic domain, and blocks the IFNα, IL-12/IL-23-mediated JAK-STAT signaling pathway. QL-1200186 can inhibit the production of Th1/Th17 cell-related cytokines (such as IFNγ, IL-23), reduce immune cell activation, and has no significant effect on JAK1/2/3 kinase activity. QL-1200186 can significantly improve skin inflammation in the Imiquimod (HY-B0180)-induced psoriasis mouse model and reduce the Psoriasis Area and Severity Index (PASI) score. QL-1200186 can be used in the study of autoimmune diseases such as psoriasis and systemic lupus erythematosus (SLE).

Zharp1-211 is a RIPK1 kinase inhibitor with an EC₅₀ of 53 nM and a K_d of 8.7 nM. Zharp1-211 reduces IFN-γ-induced STAT1 activation. Zharp1-211 can be used in the research of graft-versus-host disease and colon cancer.

IFN-α Receptor Recognition Peptide 1 (IRRP1) is an amino acid synthetic peptide and also a regulator of IFN-α Receptor. IFN-α Receptor Recognition Peptide 1 binds to IFNAR2, enhances the binding capacity of IFN-α receptor, and slightly increases the IFN-α-induced growth inhibitory activity. IFN-α Receptor Recognition Peptide 1 inhibits IFN-α-induced STAT1 phosphorylation and STAT-DNA binding by blocking the activation of IFNAR by IFN-α. IFN-α Receptor Recognition Peptide 1 increases the occupancy of IFN-α on cell surface receptors, enhances the phosphorylation activation of ISGF3, and elevates IFN-α-induced antiviral activity. IFN-α Receptor Recognition Peptide 1 can be used in studies related to encephalomyocarditis virus infection.

Biflorin has antimicrobial, antitumor, antiinflammatory and antimutagenic activities. Biflorin is found in the roots of Capraria biflora L.

CDK8-IN-2 is an orally active CDK8 inhibitor of an IC₅₀ values of 0.010 μM. CDK8-IN-2 shows a CDK19 IC₅₀ value of 0.026 μM. CDK8-IN-2 inhibits phospho-STAT1, a pharmacodynamic biomarker of CDK8. CDK8-IN-2 inhibits WNT pathway activity. CDK8-IN-2 can be used for the research of colorectal carcinoma.

ITA-5 is a TBK1 inhibitor based on the structure of itaconic acid. can significantly inhibit the secretion of IFN-β. ITA-5 can inhibit the phosphorylation of TBK1, IRF3, and STAT1. ITA-5 can be used for research on autoimmune diseases and excessive inflammation.

Apoptosis inducer 55 (Compound 10) is an Apoptosis inducer. Apoptosis inducer 55 induces rapid apoptosis via the intrinsic pathway. Apoptosis inducer 55 potently inhibits several signaling cascades including AKT, ERK1/2, STAT1, STAT3, and S6K. Apoptosis inducer 55 has anti-cancer activity against melanoma.