STAT3 Inhibitor

Ac-GpYLPQTV-NH2 is a STAT3 inhibitor with an IC₅₀ value of 0.33 μM. Ac-GpYLPQTV-NH2 has antitumor activity.

Cucurbitacin R is an orally active anti-inflammatory agent. Cucurbitacin R is isolated from the roots of Cayaponia tayuya. Cucurbitacin R inhibits Cyclooxygenase-2. Cucurbitacin R inhibits Interleukin-6-induced STAT3 activation and cytokine production, blocks NF-κB activation, and selectively prevents NFAT nuclear translocation without affecting Calcineurin activity. Cucurbitacin R inhibits TNF-α production and Nitric-oxide synthase-2 expression. Cucurbitacin R reduces joint damage, soft tissue swelling, paw edema, ear edema, inflammatory cell infiltration, and epithelial thickness. Cucurbitacin R can be used for research on arthritis and delayed-type hypersensitivity.

Eupalinolide K, a sesquiterpene lactones compound from Eupatorium lindleyanum, is a STAT3 inhibitor. Eupalinolide K is a Michael reaction acceptor (MRA) .

Laricitrin is a natural product with multiple biological activities. Laricitrin inhibits the phosphorylation and DNA-binding activity of STAT3, and downregulates the expression of IL-10. Laricitrin acts as an immunomodulator to regulate the differentiation, maturation and function of dendritic cells (DCs). Laricitrin inhibits the migration and invasion of lung cancer cells, and ameliorates lung cancer progression. Laricitrin can be used in research related to hypertension and lung cancer.

Niclosamide (BAY2353) monohydrate is an orally active antihelminthic agent used in parasitic infection research. Niclosamide monohydrate is a STAT3 inhibitor with an IC₅₀ of 0.25 μM in HeLa cells. Niclosamide monohydrate has biological activities against cancer, and inhibits DNA replication in Vero E6 cells.

SD-1008 is a potent JAK inhibitor. SD-1008 inhibits tyrosyl phosphorylation of STAT3, JAK2 and Src. SD-1008 also reduces STAT3-dependent luciferase activity. SD-1008 enhances apoptosis induced by Paclitaxel in ovarian cancer cells via directly blocking the JAK-STAT3 signaling pathway.

Sorafenib-d4 (Bay 43-9006-d4) is the deuterated-labeled Sorafenib (HY-10201). Sorafenib (Bay 43-9006) is a potent oral active multikinase inhibitor. Sorafenib blocks autophosphorylation and activity of receptor tyrosine kinases (VEGFR-2, VEGFR-3) and RAF family kinases, thereby suppressing the RAF/MEK/ERK and PI3K/Akt pathways, inhibiting STAT3 phosphorylation, and selectively inhibiting the MAPK pathway in cancer cells. Sorafenib induces cell cycle arrest, autophagy, apoptosis, and PARP cleavage, reduces Bcl-2, Bcl-XL, cyclin D1 levels, and activates Bak and Bax. Sorafenib inhibits tumor growth and metastasis in mouse and rat models. Sorafenib can be used for cancer research, such as colon, breast, non-small-cell lung cancer (NSCLC), ovarian, pancreatic, melanoma, colorectal and hepatocellular carcinoma.

HGR4113 is an orally active anti-inflammatory/antioxidant agent with improved glucose metabolism. HGR4113 inhibits STAT3 phosphorylation, suppresses Th17 differentiation and IL-17 production, reduces oxidative phosphorylation activity, and promotes the differentiation of regulatory T cells among splenic CD4⁺ T cells. HGR4113 inhibits LPS (HY-D1056)-induced JNK phosphorylation, production of NO, PGE₂ and pro-inflammatory cytokines, expression of iNOS and COX-2, as well as nuclear translocation of NF-κB in macrophages, while induces HO-1 expression by activating nuclear translocation of Nrf2. HGR4113 can be used in the research of inflammatory diseases such as type 2 diabetes and Sjögren's syndrome.

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).

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.

STAT3-IN-8 (compound H172) is a potent STAT3 inhibitor. STAT3-IN-8 has the potential for cancer research.

YSY01A is a proteasome inhibitor that can suppress cancer cell survival by inducing apoptosis (Apoptosis). Its IC₅₀ values are 51.0 nM for HEK293T, 9.2 nM for A549, 5.2 nM for MCF-7, 8.9 nM for MGC-803, and 35.4 nM for PC-3M cells. Additionally, YSY01A eliminates constitutive STAT3 signaling by downregulating gp130 and JAK2 in human A549 lung cancer cells. YSY01A holds promise for research in the field of cancer therapy.

c-Met-IN-24 (compound 3g) is a dual-target inhibitor of STAT-3 (=4.7 μM) and c-MET (=12.67 μM) with anticancer activity. c-Met-IN-24 arrests the G2/M cell cycle and induces apoptosis in SNB-75 cells. c-Met-IN-24 can be used in the study of central nervous system cancers.

RET-IN-2 is a selective RET inhibitor with an IC₅₀ of 61.2 nM. RET-IN-2 inhibits the phosphorylation of RET and its downstream STAT3 and AKT proteins in BaF3/CCDC6-RET cells. RET-IN-2 inhibits the proliferation of RET fusion-positive cells. RET-IN-2 can be used for cancer-related research.

DM245 is an EPAC1 activator and STAT3 phosphorylation inhibitor with a target pIC₅₀ of 4.801. DM245 activates EPAC1 to increase Rap1-GTP levels, with no activation of EPAC2 or PKA. DM245 reduces IL-6/IL-6Rα-evoked STAT3 phosphorylation in endothelial cells. DM245 suppresses TGF-β1-induced fibroblast-to-myofibroblast transition, reducing αSMA and Collagen I levels. DM245 exhibits minimal cytotoxicity in normal human lung fibroblasts, with negligible loss of intact nuclei after 72 h exposure.

IM-12 GMP is IM-12 (HY-12292) produced by using GMP guidelines. GMP small molecules works appropriately as an auxiliary reagent for cell therapy manufacture. IM-12 is an orally active anti-inflammatory agent that targets and inhibits the NF-κB and STAT3 signaling pathways. IM-12 activates the Wnt signaling pathway and promotes the nuclear translocation of β-catenin by inhibiting GSK3β, while also blocking the tyrosine kinase activity of p210BCR/ABL. IM-12 reduces the levels of IL-6, IL-17, NO, prostaglandin E2, iNOS and COX-2, and induces ER stress, Ca²⁺ release, autophagy and apoptosis. IM-12 is heat-sensitive and does not induce autophagy in IM-resistant p210BCR/ABL^T315I mutant cells. IM-12 is also a component of the 5iLA medium used for naive pluripotent stem cell research. IM-12 has been applied in studies related to carrageenan (HY-125474)-induced hind paw edema, TNBS-induced colitis, and acute and chronic myeloid leukemia.

Usenamine A is an orally active natural dibenzofuran compound with multiple biological activities such as anti-inflammatory and anticancer effects. Usenamine A inhibits the AKT/mTOR/STAT3/ID1 signaling axis and induces ubiquitin-proteasome degradation of ID1. Usenamine A targets the TNF-TNFR2 complex, inhibits RGS2, and interferes with Myosin-9/actin cytoskeleton remodeling. Usenamine A induces apoptosis, autophagy and ROS-mediated endoplasmic reticulum stress in cancer cells, inhibits cancer cell proliferation and invasion, and reduces the production of pro-inflammatory cytokines. Usenamine A alleviates arthritis-related symptoms. Usenamine A can be used in studies related to liver cancer, non-small cell lung cancer, rheumatoid arthritis and ankylosing spondylitis.

STAT3-IN-38 (Compound 4m) is an inhibitor of STAT3 (K_D of rhSTAT3: 45.33  µM). STAT3-IN-38 binds to the SH2 domain of STAT3 protein and suppresses the STAT3’s phosphorylation at site pTyr705 as well as its downstream genes (Survivin and Mcl-1). STAT3-IN-38 could block cell-cycle and induce Apoptosis in colorectal cancer cells.

STAT3-IN-29 (Compound B20) is an inhibitor for STAT3. STAT3-IN-29 inhibits the proliferation of HaCaT cell with IC₅₀ of 0.09 µM, ameliorates the IMQ-induced psoriasis in mouse models.

VEGFR-2/STAT-3-IN-1 (Compound 9f) is a dual inhibitor for VEGFR-2 (IC₅₀=26.3 nM) and STAT-3 (IC₅₀=5.63 nM). VEGFR-2/STAT-3-IN-1 inhibits the proliferation of cancer cells PANC1 and PC3 with IC₅₀ of 0.14 and 0.10 µM. VEGFR-2/STAT-3-IN-1 induces apoptosis in PC3.