STAT3 Inhibitor

STAT3-IN-53 (Compound L20) is a STAT3 inhibitor with a K_d value of 6.16 μM. STAT3-IN-53 binds directly to the SH2 domain of STAT3, inhibits phosphorylation at the Y705 site without affecting the total STAT3 protein level, and suppresses the IL-6/JAK/STAT3 pathway. STAT3-IN-53 downregulates the transcription and expression of cyclin-D1 and c-Myc. STAT3-IN-53 induces cell cycle arrest and promotes Apoptosis. STAT3-IN-53 exhibits anticancer activity against colorectal cancer.

STAT3-IN-51 is a STAT3 inhibitor that directly binds to the STAT3 SH2 domain. STAT3-IN-51 induces apoptosis, ferroptosis, and immunogenic cell death (ICD) to potentiate anti-tumor immunity. STAT3-IN-51 inhibits STAT3 activation (phosphorylation, p-STAT3) and its downstream signaling. STAT3-IN-51 induces ROS generation, decreases Bcl-2 expression, disruptes mitochondrial function, suppresses GPX4 activity, and promotes lipid peroxidation. STAT3-IN-51 can be used for the study of colorectal carcinoma, breast adenocarcinoma, non-small cell lung cancer (NSCLC) and Cisplatin (HY-17394)-resistant pulmonary adenocarcinoma.

EGFR/STAT3-IN-2 is an inhibitor of EGFR tyrosine kinase and STAT3 signaling. EGFR/STAT3-IN-2 induces Apoptosis and G0/G1 cell cycle arrest. EGFR/STAT3-IN-2 exhibits selective anticancer activity against lung adenocarcinoma. EGFR/STAT3-IN-2 can be used for research on non-small cell lung cancer.

Ascochlorin (Ilicicolin D), an isoprenoid antibiotic, mediates its anti-tumor effects predominantly through the suppression of STAT3 signaling cascade. Ascochlorin induces apoptosis. Anti-inflammatory activity.

NSC 850745 is a selective and potent c-Met/STAT3 inhibitor with IC₅₀ values of 210 and 670 nM. NSC 850745 can inhibit cell proliferation, induce G2/M phase arrest and induce apoptosis. NSC 850745 can downregulate AKT-1, VEGF and Bcl-2 expression and upregulate p53, Bax and caspase expression. NSC 850745 can be used for the research of cancer, such as leukemia and colon cancer.

15-Keto-prostaglandin E2-d₉ is the d₉ labeled 15-keto-Prostaglandin E2 (HY-113205). 15-keto-Prostaglandin E2 (15-keto-PGE2) is an endogenous PGE₂ metabolite. 15-keto-Prostaglandin E2 inhibits STAT3 activation by binding to the Cys259 residue of STAT3. 15-keto-Prostaglandin E2 binds to and stabilizes EP2 and EP4 receptors. 15-keto-Prostaglandin E2 inhibits the growth and progression of breast cancer cells. 15-keto-Prostaglandin E2 activates PPAR-γ and promotes fungal growth. 15-keto-Prostaglandin E2 disrupts glomerular vascularization during zebrafish development and reduces the surface area of the glomerular filtration barrier.

JAK2-IN-21 is a Janus kinase 2 (JAK2) inhibitor with an IC₅₀ of 12.25 nM. JAK2-IN-21 inhibits the JAK2/STAT3/STAT5 tumor-promoting signaling pathway and reduces JAK2 protein expression. JAK2-IN-21 exhibits selective cytotoxicity against HPV-positive cancer cells and induces cancer cell apoptosis. JAK2-IN-21 can be used in the research of HPV-positive cervical cancer.

STAT3/NF-κB-IN-2 is a dual STAT3/NF-κB inhibitor that exhibits antiproliferative, antimigratory and anti-invasive activities in cancer cells. STAT3/NF-κB-IN-2 inhibits the transcriptional activities of NF-κB and STAT3, binds to the STAT3-SH2 domain, and blocks STAT3 dimerization. STAT3/NF-κB-IN-2 can be used in studies related to triple-negative breast cancer.

PI3K/Akt/mTOR-IN-7 is an AKT/mTOR and JAK2/STAT3 inhibitor. PI3K/Akt/mTOR-IN-7 restores p-Akt, p-mTOR, and p-STAT3 expression, reduces pro-apoptotic Caspase-3 mRNA expression. PI3K/Akt/mTOR-IN-7 reduces intracellular ROS accumulation and inhibits NO production. PI3K/Akt/mTOR-IN-7 can be used for research on stroke, Alzheimer's disease and Parkinson's disease.

CHI3L1-IN-7 is a selective CHI3L1 inhibitor with a K_d of 7.40 μM and an IC₅₀ of 15.4 μM. CHI3L1-IN-7 blocks CHI3L1's interaction with galectin-3, inhibits STAT3 phosphorylation, reduces the viability of multicellular 3D glioblastoma spheroids. CHI3L1-IN-7 can be used for the research of glioblastoma and CHI3L1-mediated tumor immune regulation.

PROTAC c-Met degrader-5 is an orally active c-Met PROTAC degrader. PROTAC c-Met degrader-5 induces c-Met degradation via Cullin-CRBN, with a DC₅₀ value of 0.32 nM, and inhibits the phosphorylation of c-Met and its downstream signaling molecule STAT3. PROTAC c-Met degrader-5 inhibits cancer cell proliferation, migration and invasion, induces apoptosis, alters cell cycle distribution, and suppresses the growth of EBC-1 xenograft tumors. PROTAC c-Met degrader-5 can be used to study MET-driven cancers as well as Tepotinib (HY-14721)-resistant cancers harboring c-Met^D1228N and c-Met^Y1230H mutations.

NF-κB/STAT3/iNOS-IN-1 is a NF-κB/STAT3/iNOS inhibitor. NF-κB/STAT3/iNOS-IN-1 reduces the expression of inflammatory mediators TNF-α, IL-1β, IL-6, IL-8 and COX-2. NF-κB/STAT3/iNOS-IN-1 upregulates the expression of epithelial barrier-related proteins E-cadherin, Occludin and Zonula occludens-1. NF-κB/STAT3/iNOS-IN-1 alleviates disease severity and histopathological damage in mouse colitis models. NF-κB/STAT3/iNOS-IN-1 can be used for the research of inflammatory bowel disease (colitis).

AUH-6-96 is a JAK/STAT signaling inhibitor. AUH-6-96 reduces Unpaired-induced transcriptional activity in Drosophila cells and blocks tyrosine phosphorylation of STAT92E. AUH-6-96 blocks both constitutive and IL-6-induced phosphorylation of STAT3. AUH-6-96 decreases the level of tyrosine-phosphorylated JAK3. AUH-6-96 induces cancer cell Apoptosis by downregulating the expression of anti-apoptotic genes downstream of STAT3. AUH-6-96 selectively reduces the viability of cancer cells with abnormal JAK/STAT signaling pathway. AUH-6-96 is applicable to related research on Hodgkin's lymphoma, breast cancer, and prostate cancer.

SNX631 is an orally active and selective CDK8/CDK19 inhibitor. SNX631 reduces the phosphorylation of STAT1/STAT3 S727, and upregulates miR-21-5p, miR-21-3p and miR-221 in cancer cells. SNX631 transcription-independently inhibits meiotic resumption in mouse oocytes, blocks nuclear envelope breakdown, first polar body extrusion and mitochondrial expansion and aggregation, with no cytotoxicity. SNX631, in combination with Lapatinib (HY-50898) or Trastuzumab (HY-P9907), synergistically inhibits cancer cell growth, upregulates the tumor suppressor BTG2, prevents Lapatinib-induced upregulation of oncogenic miRNAs, overcomes drug resistance, reduces the infiltration of αSMA+ stromal fibroblasts and ARG1+ M2 macrophages, and exhibits favorable biosafety. SNX631 can be used in studies related to HER2-positive breast cancer and cancer.

JAK2/STAT3-IN-2 is an orally active JAK2/STAT3 inhibitor. JAK2/STAT3-IN-2 inhibits the phosphorylation of tyrosine residues in JAK2 and STAT3, blocks downstream signal transduction, disrupts the dimerization and nuclear translocation of STAT3, and suppresses pro-inflammatory transcriptional activity. JAK2/STAT3-IN-2 inhibits the expression of IL-17A and IL-17F, reduces immune cell infiltration, and inhibits the production of NO simultaneously. JAK2/STAT3-IN-2 exerts a protective effect in a mouse model of ulcerative colitis induced by DSS (HY-116282C). JAK2/STAT3-IN-2 can be used for the research of ulcerative colitis.

NW16 is an orally active inhibitor for STAT3 with K_d of 11.0 μM. NW16 arrests the cell cycle at S phase, induces apoptosis in HCT116, and inhibits the proliferation of cancer cell HCT116, A549, and B16 with IC₅₀s of 0.28, 1.22, and 9.86 μM, respectively. NW16 induces the production of ROS, inhibits the PI3K/AKT signaling pathway, and thus exhibits antitumor efficacy in mouse model.

NS06 is a dual-target inhibitor of STAT3 and HDAC, with a K_d of 5.82 μM for human STAT3, an IC₅₀ of 129.1 nM for human HDAC1, an IC₅₀ of 451.2 nM for human HDAC3, and an IC₅₀ of 230.4 nM for human HDAC6. NS06 binds to STAT3 to inhibit its phosphorylation without altering the total STAT3 level; it inhibits the enzymatic activity of HDAC via coordination with Zn²⁺ at the catalytic center of HDAC1 and increases the acetylation level of histone H3. NS06 induces cell apoptosis, inhibits cancer cell migration and colony formation, and exhibits antiproliferative activity against solid tumor cells and 3D tumor spheroid models. NS06 is applicable to solid tumor-related research.

MRC-G-001 is a Genipin (HY-17389) derivative with an IC₅₀ of 117 μM against A549 cancer cells. MRC-G-001 inhibits the phosphorylation of EGFR, JAK1, and STAT3, and modulates epithelial-mesenchymal transition (EMT)-related protein expression, thereby attenuating cell migration and invasion. MRC-G-001 induces cell cycle arrest and cell apoptosis. MRC-G-001 can be used for the study of cancers such as non-small-cell lung cancer.

STAT3-IN-33 (compound 7f) is a potent STAT3 inhibitor with anti-cancer activity. STAT3-IN-33 exhibits antiproliferative activity in HCT116, MCF-7, and MDA-MB-231 cells, with IC₅₀s of 6.44, 3.29, and 4.86 μM, respectively. STAT3-IN-33 can be used for breast and colon cancer research.

CDK6/9-IN-2 is a highly active dual inhibitor of CDK6 (IC₅₀ = 15 nM) and CDK9 (IC₅₀ = 22 nM). CDK6/9-IN-2 is selective for CDK2, CDK8, and CDK11. CDK6/9-IN-2 inhibits the proliferation of HaCaT cells induced by IFN-γ/TNF-α and suppresses the STAT3 pathway and the expression of inflammatory factors. CDK6/9-IN-2 can alleviate psoriatic dermatitis and is useful in psoriasis research.