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.

Itacitinib (INCB039110) is an orally active selective inhibitor of JAK1 with an IC₅₀ value of 2 nM for human JAK1. Itacitinib inhibits IFN-γ-mediated phosphorylation of STAT1 and downstream pro-inflammatory signaling pathways. Itacitinib reduces the frequency and number of splenic neutrophils in mouse models, downregulates the levels of pro-inflammatory cytokines and chemokines, and inhibits pro-inflammatory gene expression pathways. Itacitinib improves survival rate and clinical scores in mouse models of hemophagocytic lymphohistiocytosis (HLH), and also suppresses metastasis in NSCLC models with high Rab1A expression. Itacitinib can be used for research on hemophagocytic lymphohistiocytosis and non-small cell lung cancer.

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).

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.

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.

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 dual degrader of CDK8 and cyclin C HyT, with DC₅₀ values of 2.52 μM and 2.64 μM, respectively. LL-K8-22 inhibits phosphorylation of STAT1 Ser 727, phosphorylation of the C-terminal domain Ser 2/5 of RNA polymerase II, and phosphorylation of Rb. LL-K8-22 represses E2F- and MYC-driven transcriptional programs and exhibits antiproliferative effects. LL-K8-22 synchronously induces proteasome-dependent selective degradation of CDK8 and cyclin C without degrading CDK19, other CDK family members, or other cyclins. LL-K8-22 can be used in the research of triple-negative breast cancer and colon cancer.

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).

LRRK2 inhibitor 1 is a LRRK2 inhibitor. LRRK2 inhibitor 1 blocks STAT1 phosphorylation and the expression of interferon-stimulated genes, and inhibits intracellular innate immune responses. LRRK2 inhibitor 1 enhances oncolytic virus infection, replication and viral protein expression in tumor cells, promotes tumor cell apoptosis, and cooperates with oncolytic viruses to reduce tumor cell viability. LRRK2 inhibitor 1 enhances the oncolytic activity of multiple oncolytic viruses, and inhibits the growth of glioma xenografts when used in combination with oncolytic viruses. LRRK2 inhibitor 1 can be used in research related to various cancers such as lung cancer, colorectal cancer and liver cancer.

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.

Itacitinib adipate (INCB039110 adipate) is an orally active JAK1-selective inhibitor. Itacitinib adipate inhibits IFN-γ-mediated phosphorylation of STAT1 and downstream pro-inflammatory signaling pathways. Itacitinib adipate reduces the frequency and number of splenic neutrophils in mouse models, downregulates the levels of pro-inflammatory cytokines and chemokines, and inhibits pro-inflammatory gene expression pathways. Itacitinib adipate improves survival rate and clinical scores in mouse models of hemophagocytic lymphohistiocytosis (HLH), and also suppresses metastasis in NSCLC models with high Rab1A expression. Itacitinib adipate can be used for research on hemophagocytic lymphohistiocytosis and non-small cell lung 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.