8-Epixanthatin is a potential colchicine binding site inhibitor isolated from Xanthium chinese Mill. 8-Epixanthatin can inhibit the activation of STAT3, induce apoptosis, and has anti-tumor activity[1].
(R)-Lisofylline ((R)-Lisophylline) is a (R)-enantiomer of the metabolite of Pentoxifylline with anti-inflammatory properties. (R)-Lisofylline is a lysophosphatidic acid acyltransferase inhibitor with an IC50 of 0.6 µM and interrupts IL-12 signaling-mediated STAT4 activation. (R)-Lisofylline has the potential for type 1 diabetes, autoimmune disorders research[1][2].
Pimozide D4 (R6238 D4) is a deuterium labeled Pimozide. Pimozide is a dopamine receptor antagonist, with Kis of 1.4 nM, 2.5 nM and 588 nM for dopamine D2, D3 and D1 receptors, respectively, and also has affinity at α1-adrenoceptor, with a Ki of 39 nM; Pimozide also inhibits STAT3 and STAT5[1][2][3].
HJC0152 (free base) is an orally active and potent inhibitor of STAT3. HJC0152 (free base) inhibits cell cycle progression and induces apoptosis. HJC0152 (free base) significantly suppresses MDA-MB-231 xenograft tumor growth in mice[1].
Brevilin A is a sesquiterpene lactone isolated from Centipeda minima with anti-tumor activity. Brevilin A is a selective inhibitor of JAK-STAT signal pathway by attenuating the JAKs activity and blocking STAT3 signaling (IC50 = 10.6 µM) in Cancer Cells. Brevilin A induces apoptosis and autophagy via mitochondrial pathway and PI3K/AKT/mTOR inactivation in colon adenocarcinoma cell CT26[1][2].
SH-4-54 is a most potent, small molecule, nonphosphorylated STAT inhibitor, with KDs of 300, 464 nM for STAT3 and STAT5, respectively.
NSC-370284 is a selective inhibitor of ten-eleven translocation 1 (TET1). NSC-370284 significantly inhibits the level of TET1 expression via targets STAT3/5. NSC-370284 has low cytotoxicity[1].
Napabucasin is a STAT3 inhibitor which blocks stem cell activity in cancer cells.
Colivelin is a neuroprotective peptide and activator of STAT3.
Picroside I is the major ingredient of Picrorhiza kurroa. Picrorhiza kurroa is a high value medicinal herb due to rich source of hepatoprotective metabolites, Picroside-I and Picroside-II[1]. 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[2].
A novel small molecule STAT3 inhibitor that inhibits STAT3 DNA binding activity with IC50 of 1.16 uM, binds to the STAT3 coiled-coil domain (CCD); also inhibits G-CSF-induced STAT3 phosphorylation in AML cell lines with IC50 of 0.8-1.9 uM,
AS2863619 free base enables conversion of antigen-specific effector/memory T cells into Foxp3+ regulatory T (Treg) cells for the treatment of various immunological diseases. AS2863619 free base is a potent, orally active cyclin-dependent kinase 8 (CDK8) and CDK19 inhibitor with IC50s of 0.61 nM and 4.28 nM, respectively. STAT5 activation enhanced by AS2863619 free base inhibition of CDK8/19, which consequently activates the Foxp3 gene[1].
WP1066 is an inhibitor of JAK2 and STAT3, and also shows effect on STAT5 and ERK1/2, without affecting JAK1 and JAK3.
A novel selective STAT3 inhibitor that inhibits JAK2-STAT3 activation but has no effects on other transcription factors such as NF-κB, and kinases such as AKT, ERK, and c-Src; inhibits STAT3 phosphorylation, dimerization and nuclear translocation, downregulates STAT3-modulated gene expression and induces MM cell apoptosis; delays tumor growth in MM xenograft models (30mg/kg); orally active.
XZH-5 is a small moelcule that inhibits constitutive and interleukin-6-induced STAT3 phosphorylation, inhibits STAT3 DNA binding ability and downregulation of STAT3 downstream genes; inhibits downregulation of STAT3 downstream genes, such as Bcl-2, Bcl-xL, Cyclin D1 and Survivin, demonstrates blockade of STAT3 phosphorylation in human rhabdomyosarcoma cells with apoptosis and suppresses colony-forming ability and cell migration; blocks IL-6-induced STAT3 phosphorylation and nuclear translocation but not the stimulation of STAT1 phosphorylation by IFN-γ.
PROTAC STAT3 degrader-2 is a selective and efficacious PROTAC degrader of STAT3 protein with a DC50 of 3.54 μM in Molm-16 Cell. PROTAC STAT3 degrader-2 has the potential for cancer research[1].
AS2863619 enables conversion of antigen-specific effector/memory T cells into Foxp3+ regulatory T (Treg) cells for the treatment of various immunological diseases. AS2863619 is a potent, orally active cyclin-dependent kinase 8 (CDK8) and CDK19 inhibitor with IC50s of 0.61 nM and 4.28 nM, respectively. STAT5 activation enhanced by AS2863619 inhibition of CDK8/19, which consequently activates the Foxp3 gene[1].
AC-4-130 is a novel, potent STAT5 SH2 domain inhibitor, binds to and efficiently blocks STAT5 activation and subsequent transcriptional activity, shows high selectivity for STAT5 over STAT1 and STAT3; disrupts STAT5 activation, dimerization, nuclear translocation, and STAT5-dependent gene transcription; substantially impairs the proliferation and clonogenic growth of human AML cell lines and primary FLT3-ITD+ AML patient cells in vitro and in vivo; synergistically increases the cytotoxicity of the JAK1/2 inhibitor Ruxolitinib and the p300/pCAF inhibitor Garcinol in vivo.
Peruvoside is a potent inhibitor of Src, PI3K, JNK, STAT, and EGFR. Peruvoside induces apoptosis and autophagy and possesses a broad spectrum of anticancer activity in breast, lung, liver cancers and leukemia. Peruvoside is a broad-spectrum and potent antiviral activity against positive-sense RNA viruses. Peruvoside sensitizes Gefitinib (HY-50895)-resistant tumour cells (A549, PC9/gef and H1975) to Gefitinib[1][2][3][4].
STAT3-IN-11 (7a) is a selective STAT3 inhibitor that inhibits the phosphorylation of STAT3 at site pTyr705. STAT3-IN-11 inhibits the phosphorylation of downstream genes (Survivin and Mcl-1) without affecting its upstream tyrosine kinases (Src and JAK2) levels and p-STAT1 expression. STAT3-IN-11 can induce cancer cell apoptosis, which is potential for the discovery of effective STAT3 inhibitors and antitumor agents against cancers[1].
Cenisertib (AS-703569) is a multi-kinase inhibitor that blocks the activity of Aurora-kinase-A/B, ABL1, AKT, STAT5 and FLT3. Cenisertib induces major growth-inhibitory effects by blocking the activity of several different molecular targets in neoplastic mast cells (MC)[1]. Cenisertib inhibits tumor growth in xenograft models of pancreatic, breast, colon, ovarian, and lung tumors and leukemia[2].
W1131 is a potent STAT3 inhibitor, triggering ferroptosis. W1131 suppresses cancer progression in gastric cancer cell subcutaneous xenograft model, organoids model, and PDX model. W1131 effectively alleviates chemical resistance of cancer cells to 5-FU (HY-90006). W1131 regulates cell cycle, DNA damage response, and oxidative phosphorylation, including IL6-JAK-STAT3 pathway and ferroptosis pathway[1].
BP-1-102 is an orally available, small-molecule inhibitor of transcription factor Stat3, with an IC50 of 6.8 μM.
MNK8 is a potent STAT3 (signal transducer and activator of transcription 3) inhibitor. MNK8 inhibits STAT3 activation and reduced its DNA binding ability. MNK8 shows good growth inhibition against hepatocellular carcinoma (HCC) cells. MNK8 induces apoptosis in HCC cells. MNK8 reduces prosurvival proteins expression and migration/invasion of HCC cells[1].
ROCK2-IN-7 is a kinase inhibitor targeting to ROCK2. ROCK2-IN-7 inhibits ROCK2/pSTAT3 Signaling. ROCK2-IN-7 suppresses systemic immunity activation and attenuates inflammation in psoriasis model[1].
(+)-Ochromycinone is a natural antibiotic that potently inhibits STAT3. (+)-Ochromycinone is used in the researches of cancers and psoriasis[1][2].
SC-43, a Sorafenib derivative, is a potent and orally active SHP-1 (PTPN6) agonist. SC-43 inhibits the phosphorylation of STAT3 and induces cell apoptosis. SC-43 has anti-fibrotic and anticancer effects[1][2].
STAT3-IN-18 (compound SPP) is a platinum (IV) complex with an axial ligand derived from sandalwood. STAT3-IN-18 inhibits the JAK2-STAT3 pathway in breast cancer (BC) cells, with anti-proliferative activity. STAT3-IN-18 activates caspase-3 and increases cleaved polyADP-ribose polymerase to induce apoptosis. STAT3-IN-18 promotes maturation and antigen presentation of dendritic cells and demonstrates safety in vivo.
(S)-PM-43I is a potent STAT6 inhibitor and can reduce STAT6 phosphorylation level. (S)-PM-43I can be used in allergic lung disease, allergic rhinitis, chronic pulmonary obstructive disease and cancer research[1].
BD750, an effective immunosuppressant and a JAK3/STAT5 inhibitor, inhibits IL-2-induced JAK3/STAT5-dependent T cell proliferation, with IC50 values of 1.5 μM and 1.1 μM in mouse and human T cells, respectively[1][2].