STAT6 Inhibitor

AS1517499 is a potent and brain-permeable STAT6 phosphorylation inhibitor with an IC₅₀ of 21 nM.

Ritlecitinib (PF-06651600) is a highly selective, orally active, irreversible covalent JAK3 inhibitor (IC₅₀=33 nM) without inhibitory activity towards JAK1, JAK2, and TYK2 (IC₅₀ >10 μ M). Ritlecitinib rapidly inactivates the JAK3 kinase, and blocks signaling and downstream STAT phosphorylation mediated by common gamma chain cytokines such as IL-2 and IL-15. Ritlecitinib can inhibit Th1/Th17 cell differentiation and function, and effectively suppress preclinical animal models such as alopecia areata, adjuvant-induced arthritis (AIA), and experimental autoimmune encephalomyelitis (EAE).

Stapokibart (CM310) is a humanized monoclonal antibody targeting IL-4Rα (K_D values of 0.25 nM, 1.50 nM, and 2.75 nM for human, cynomolgus monkey, and rat IL-4Rα, respectively). Stapokibart effectively blocks the interaction of cytokines IL-4 and IL-13 with their co-receptor subunit IL-4Rα. Stapokibart reduces IL-4 and IL-13 mRNA, inhibits CD23 upregulation, and inhibits IL-4 and IL-13-induced STAT6 activation. Stapokibart improves inflammation (airway inflammation, rhinitis, dermatitis).

BP79 is a potent TSLP receptor inhibitor. BP79 disrupts TSLP-mediated ternary complex formation, blocks TSLPR-IL7Rα co-localization, binds and stabilizes TSLPR, and inhibits phosphorylated STAT3/6. BP79 suppresses immune cell infiltration, secretion of IL-13, IL-4. BP79 can be used for the research of inflammation diseases, such as atopic dermatitis, allergic asthma, and allergic rhinitis.

YYSW001 is a selective and orally acrive JAK1 inhibitor with an IC₅₀ of 6 nM and a Kd of 32.32 μM. YYSW001 blocks JAK1-dependent phosphorylation of STAT6, as well as IL-6-induced phosphorylation of STAT3. YYSW001 suppresses pro-inflammatory cytokine levels, reduces paw swelling, lowers clinical arthritis scores, alleviates joint damage and decreases bone loss. YYSW001 is applicable for the research of rheumatoid arthritis.

YM-341619 (AS1617612) is a potent and orally active STAT6 inhibitor with an IC₅₀ of 0.70 nM. YM-341619 inhibits Th2 differentiation in mouse spleen T cells induced by IL-4 (IC₅₀=0.28 nM) without affecting Th1 cell differentiation. YM-341619 is a promising compound for the the research of allergic diseases, such as allergic asthma.

STAT6-IN-5 (compound 84) is a STAT6 inhibitor (IC₅₀=0.24 μM), which can be used for the research of inflammatory diseases and allergic diseases (e.g. atopic dermatitis).

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.

STAT6-IN-4 (Ex. 78) is a STAT6 inhibitor, with an IC₅₀ of 0.34 μM. STAT6-IN-4 can be used in the research of diseases such as inflammatory and allergic diseases.

AS1810722 is an orally active and potent STAT6 inhibitor with an IC₅₀ of 1.9 nM. AS1810722 shows a good profile of CYP3A4 inhibition. AS1810722, a derivative of fused bicyclic pyrimidine, has the potential for allergic diseases such as asthma and atopic diseases research.

Rademikibart (CBP-201) is a human monoclonal antibody targeting IL-4Rα and IL-4Rα inhibitor with a K_D of 20.7 pM when binding to human IL-4Rα epitopes. Rademikibart does not bind to IL-4Rα from other species. Rademikibart inhibits IL-4 and IL-13-mediated STAT6 signaling, TF-1 cell proliferation and thymus activation regulated chemokine (TRAC) production. Rademikibart can be used for the research of atopic dermatitis and asthma.

UNC1062 is a highly selective tyrosine kinase (MERTK) inhibitor with an IC₅₀ of 1.1 nM (Morrison K_i = 0.33 nM). UNC1062 exhibits good selectivity for the TAM family (TYRO3 IC₅₀ = 60 nM, AXL IC₅₀ = 85 nM). UNC1062 exhibits significant anti-proliferative effects and induces apoptosis in various cancer models (such as melanoma, gastric cancer, and acute myeloid leukemia). UNC1062 inhibits multiple pathways, including MAPK/ERK, PI3K/AKT and JAK/STAT and affects the motility of head and neck squamous cell carcinoma (HNSCC) cells through the RhoA signaling pathway. UNC1062 inhibits macrophage efferocytosis, and it suitable for research on atherosclerosis.

Picroside I is the major ingredient of Picrorhiza scrophulariiflora. Picrorhiza scrophulariiflora is a high value medicinal herb due to rich source of hepatoprotective metabolites, Picroside-I and Picroside-II. Picroside I is a promising agent for the management of asthma. Picroside I reduces the inflammation significantly at its higher dose. Picroside I also downregulates pSTAT6 and GATA3 expressions. Picroside I dose-dependently increases the serum levels of IFN-γ.

Ritlecitinib (PF-06651600) tosylate is a highly selective, orally active, irreversible covalent JAK3 inhibitor (IC₅₀=33 nM) without inhibitory activity towards JAK1, JAK2, and TYK2 (IC₅₀ >10 μ M). Ritlecitinib tosylate rapidly inactivates the JAK3 kinase, and blocks signaling and downstream STAT phosphorylation mediated by common gamma chain cytokines such as IL-2 and IL-15. Ritlecitinib tosylate can inhibit Th1/Th17 cell differentiation and function, and effectively suppress preclinical animal models such as alopecia areata, adjuvant-induced arthritis (AIA), and experimental autoimmune encephalomyelitis (EAE).

STAT6-IN-10 is a STAT6 (signal transducer and activator of transcription 6) inhibitor with an EC₅₀ of 2 nM. STAT6-IN-10 can inhibit the secretion of CCL17 in human peripheral whole blood. STAT6-IN-10 can be used in the research of dermatological and respiratory system diseases.

Patiromer is an orally active, selective and non-absorbable intestinal potassium (K⁺) polymer binder that reversibly binds potassium ions in exchange for calcium (Ca²⁺). Patiromer can rapidly and continuously reduce serum potassium levels, maintain a normal blood potassium state, and reduce serum aldosterone levels. Patiromer also increases fecal potassium excretion. Patiromer is mainly used in the study of hyperkalemia associated with diseases such as chronic kidney disease, diabetes, and heart failure, and is particularly suitable for improving renin-angiotensin-aldosterone system inhibitor (RAASi) therapy.

15 (R)-Lipoxin A4 (15-epi-LXA4) is a specialized pro-resolving mediator and an acetylated derivative of COX2. 15 (R)-Lipoxin A4 is present in neurons. 15 (R)-Lipoxin A4 induces the SPM synthases ALOX12 and ALOX15, as well as the pro-resolving receptor ALX. 15 (R)-Lipoxin A4 inhibits protein kinases, including JNK1/2/3, Lyn, STAT-3 and STAT-6. 15 (R)-Lipoxin A4 enhances the release of pro-resolving mediators. 15 (R)-Lipoxin A4 alleviates the pro-inflammatory phenotype of tendon-derived stromal cells. 15 (R)-Lipoxin A4 promotes the resolution of neuroinflammation. 15 (R)-Lipoxin A4 is applicable to research related to achilles tendinitis, achilles tendon rupture and Alzheimer’s disease.

Nitroaspirin (NCX 4016) is an orally active inhibitor of ARG1 and NOS2. Nitroaspirin reduces ARG1 enzymatic activity via the STAT6-mediated signaling pathway, and feedback-inhibits the catalytic activity of NOS2 in a NO-releasing group-dependent manner. Nitroaspirin continuously releases intracellular NO, inducing redox-dependent loss of cell viability. Nitroaspirin also exerts anti-angiogenic effects by causing endothelial barrier dysfunction, and effectively inhibits the proliferation of Cisplatin (HY-17394)-resistant human ovarian cancer cells. Nitroaspirin can be used in research related to colon cancer, breast cancer and Cisplatin-resistant human ovarian cancer.

Ritlecitinib (PF-06651600) malonate is a highly selective, orally active, irreversible covalent JAK3 inhibitor (IC₅₀=33 nM) without inhibitory activity towards JAK1, JAK2, and TYK2 (IC₅₀ >10 μ M). Ritlecitinib malonate rapidly inactivates the JAK3 kinase, and blocks signaling and downstream STAT phosphorylation mediated by common gamma chain cytokines such as IL-2 and IL-15. Ritlecitinib malonate can inhibit Th1/Th17 cell differentiation and function, and effectively suppress preclinical animal models such as alopecia areata, adjuvant-induced arthritis (AIA), and experimental autoimmune encephalomyelitis (EAE).

(14S,15R)-14-Deoxyoxacyclododecindione (Compound 3) acts as an inhibitor of TGF-β-dependent Smad2/3 and IL-4-dependent STAT6, with IC₅₀ values of 90 nM and 20 nM, respectively. (14S,15R)-14-deoxyoxacyclododecindione is a potent IL-4 inhibitor with an IC₅₀
value of 20 nM. (14S,15R)-14-Deoxyoxacyclododecindione is applicable to the research of chronic inflammation and fibrotic diseases.