STAT

AS2863619 is an orally active inhibitor of cyclin-dependent kinase 8 (CDK8) and CDK19 (IC50s of 0.61 nM and 4.28 nM, respectively).

Alantolactone (Inula camphor)(Alant camphor), a sesquiterpene lactone, has potential activity against triple-negative breast Y MDA-MB-231 cells by suppressing the signal transducer and activator of transcription 3 (STAT3) signaling pathway.

Kurarinone, a flavanoid derived from shrub Sophora flavescens,Kurarinone exhibits anti-tumor, estrogenic, and anti-inflammatory activities, it also shows strong inhibitory effect on immune responses. Kurarinone may ameliorate chronic inflammatory skin diseases through the suppression of pathogenic CD4(+) T-cell differentiation and the overall immune response.

Cucurbitacin I (JSI-124), a natural compound, is a selective inhibitor of JAK2/STAT3 with anti-cancer activity.

Triacetylresveratrol (Acetyl-trans-resveratrol) has anti-cancer activity,it inhibits the phosphorylation of STAT3 and NFκB, down-regulates Mcl-1, and up-regulates Bim and Puma in pancreatic cancer cells.

Nifuroxazide (Diarlidan) is an orally available and cell-permeable nitrofuran-based antidiarrheal agent. It has the inhibitory effect against the activation of cellular STAT1/3/5 transcription.

1. Ginkgetin has anti-influenza virus and anti-fungal activities. 2. Ginkgetin has anti-inflammatory activity, can down-regulates COX-2 induction in vivo against skin inflammatory responses. 3. Ginkgetin is a good STAT3 inhibitor and may be a useful lead

inS3-54-A26 is an inhibitor of the DNA-binding domain of STAT3. inS3-54-A26 suppresses tumor growth, metastasis and the gene expression of STAT3.

JI069 (WAY-354189) is a potent STAT3 inhibitor that inhibits gp130 signaling by inducing dissociation between gp130 and JAK1.

MMPP is a novel VEGFR2 inhibitor with anti-inflammatory and potential anticancer activity, inhibits STAT3, inhibits angiogenesis via VEGFR2/AKT/ERK/NF-kappaB pathway, and can be used to alleviate myocardial injury.

JAK-STAT-IN-1 is a specific JAK-STAT inhibitor indicated for the study of autoimmune diseases.

STAT3-IN-B9 (B9) is an inhibitor of abnormal STAT3 activation and inhibits the proliferation of tumor cells including MDA-MB-468, MDA-MB-231, and DU145.

ML116 is a potent and selective STAT3 inhibitor.

(R)-Lisofylline ((R)-Lisophylline) is an inhibitor of lysophosphatidic acid acyltransferase (IC50 = 0.6 µM). (R)-Lisofylline interrupts IL-12 signaling-mediated STAT4 activation and can be used in studies about the treatment of type 1 diabetes and autoimmune disorders.

SD-36 is a selective and efficient STAT3 protein degrader (Kd=~50 nM) with antitumor activity that promotes growth inhibition and induces apoptosis by inhibiting Mcl-1 in gliomas.SD-36 inhibits the transcriptional activity of STAT3.

Cenisertib is A potent ATP-competitive multi-kinase inhibitor, showing inhibitory effects on the activity of Aurora-kinase-A/B, ABL1, AKT, STAT5, FLT3, as well as kinase inhibitors of FER and its homolog. Cenisertib inhibits the growth of tumor mast cells (MCS) by inhibiting the activity of several different molecular targets. Cenisertib also inhibits tumor growth in pancreatic, breast, colon, ovarian and lung cancer and leukemia in xenograft models.

Stafib-2 is a potent and selective inhibitor of the transcription factor STAT5b.Stafib-2 inhibits STAT5b and STAT5a with IC50 values of 82 nM and 1.7 μM, respectively.Stafib-2 has poor cell permeability.

ENMD-119 is a 2-methoxyestradiol analog with antiproliferative and antiangiogenic activity. It is suitable for inhibiting HIF-1α and STAT3 in human HCC cells.

STX-0119 is a selective, orally active STAT3 dimerization inhibitor. STX-0119 inhibits STAT3 transcription with an IC50 of 74 μM.

Ochromycinone (STA 21) is a selective STAT3 inhibitor.

BP-1-102 is an orally active, effective and specific STAT3 inhibitor. BP-1-102 binds Stat3 (Kd: 504 nM), then blocks Stat3-phosphotyrosine (pTyr) peptide interactions and Stat3 activation (4-6.8 μM), and selectively inhibits migration, survival, growth, and invasion of Stat3-dependent tumor cells. The BP-1-102-mediated inhibition of aberrantly active Stat3 in tumor cells suppresses the expression of c-Myc, Bcl-xL, Cyclin D1, Survivin, and VEGF.

HJC0152 hydrochloride (HJC0152) is a signal transducer and activator of transcription 3 (STAT3) inhibitor.

Scutellarin (Scutellarein-7-glucuronide), an active flavone isolated from Scutellaria baicalensis, can inhibit RANKL-mediated MAPK and NF-κB signaling pathway in osteoclasts, and down-regulate the STAT3 Girdin Akt signaling in HCC cells.

C188-9 (TTI-101) is a Stat3 inhibitor with an IC50 of 4-7 μM.

Diosgenin (Nitogenin) is a spirostan found in DIOSCOREA and other plants. It has favorable effects in the improvement of diabetes and regulation of lipid metabolism.

AG490 (Tyrphostin B42) is an inhibitor of EGFR (IC50: 0.1 μM). It is 135-fold more selective for EGFR than ErbB2, also inhibits JAK2 with no effect to Lyn, Lck, Syk, Btk, and Src.

Cucurbitacin B (Cuc B) has profound in vitro and in vivo antiproliferative effects against human pancreatic Y cells. It inhibited AKT signaling activation through up-regulation of PTEN. Cucurbitacin B is an effective inhibitor of HIF-1 and provide new perspectives into the mechanism of its anticancer activity. Cucurbitacin B inhibits proliferation and induces apoptosis via STAT3 pathway inhibition in A549 lung Y cells.

Fludarabine (Fludarabinum) is a fluorinated purine analog, an inhibitor of nucleic acid synthesis and an inhibitor of STAT1 activation. Fludarabine has antitumor activity and can be used for the treatment of leukemia and lymphoma.

1. Atractylenolide-I has an anti-inflammatory effect by inhibiting TNF-α and IL-6 production; ameliorates sepsis syndrome, liver and kidney functions by reduction of pro-inflammatory cytokines and LPS. 2. Atractylenolide-I significantly sensitizes the res

2-NP is a STAT1 enhancer.

WP1066 is a inhibitor of JAK2 (IC50: 2.30 μM) and STAT3 (IC50: 2.43 μM) in HEL cells; shows activity to JAK2, STAT3/5, and ERK1/2, not JAK1 and JAK3. WP1066 has been used in trials studying the treatment of Melanoma, Brain Cancer, Solid Tumors, and Central Nervous System Neoplasms.

1. Corylifol A (Corylinin) displays cytotoxic activity against HepG2 and Hep3B hepatocellular carcinoma cell lines, with IC50 values of 4.6 and 13.5 ug/ml, respectively. 2. Corylifol A and Biochanin A can be the potential uncouplers of neuronal nitric oxide synthase-postsynaptic density protein-95. 3. Corylifol A and bavachin are strong inhibitors of UDP-glucuronosyltransferase 1A1 (UGT1A1) with the inhibition kinetic parameters (Ki) values lower than 1 uM.4. Corylifol A and bakuchiol are naturally occurring potent inhibitors of hCE2, with low Ki values ranging from 0.62uM to 3.89 uM. 5. Corylifol A shows an inhibitory effect on IL-6-induced STAT3 promoter activity in Hep3B cells with IC50 values of 0.81 ± 0.15 uμ, it also inhibits STAT3 phosphorylation induced by IL-6 in Hep3B cells, suggests that corylifol A has antiinflammatory activity.

TPCA-1 (TPCA1) is an effective and specific IKK-2 inhibitor (IC50: 17.9 nM); shows >22-fold selectivity over IKK-1 and >550-fold selectivity over others kinases and enzymes.

Stattic (STAT3 Inhibitor V) is a STAT3 inhibitor (IC50=5.1 μM) that selectively inhibits STAT3 activation, dimerization, and nuclear translocation. Stattic has antitumor activity and induces apoptosis.

Cryptotanshinone (Cryptotanshinon), a STAT3 inhibitor (IC50: 4.6 μM) in a cell-free assay, strongly inhibits phosphorylation of STAT3 Tyr705, with a little effect on STAT3 Ser727, but no inhibition for STAT1 nor STAT5.

1. Atractylenolide II (2-Atractylenolide) has antimelanoma effect by inhibiting STAT3 signalling. 2. Atractylenolide II has cytotoxic/apoptotic effects may via p38 activation , ERK and Akt inactivation, p53 dependent.

AS1517499 is a potent STAT6 inhibitor with IC50 of 21 nM

STAT5-IN-1 (STAT5 Inhibitor) is a cell-permeable inhibitor which suppresses Stat5 via binding to the SH2 domain.

RO8191 (CDM-3008) (CDM-3008) is an agonist of interferon (IFN) receptor.

1. Morusin (Mulberrochromene) possesses antitumor effects of cell lines including HT-29, A549, MCF-7, and MDA-MB-231, through suppressing STAT3 and NFκB attenuation mediated apoptosis induction. 2. Morusin possesses anti-oxidant and anti-inflammatory effects.

NT157 is a small molecule tyrphostin targeting IRS protein and has the potential to inhibit IGF-1R and STAT3 signaling pathways in TME cancer cells and stromal cells, resulting in decreased cancer cell survival.

Icaritin (Anhydroicaritin) has hormone regulation activity and cardiovascular function improvement activity. Icaritin has anticancer activity, can induce S phase arrest and apoptosis, inhibit ENKL cell proliferation. Icaritin has anti-multiple myeloma activity, mainly mediated by inhibiting IL-6/JAK2/STAT3 signaling. Icaritin at low concentration (4 or 8 μMol/L) can promote rat chondrocyte proliferation and inhibit cell apoptosis, while the effect of Icaritin on rat chondrocyte at high concentration was reversed.

Corylin is a major bioactive compound isolated from Psoralea corylifolia L; it has the activity of antibiotic or anticancer.

S3I-201 (S3I-201) is a selective Stat3 inhibitor (IC50: 86±33 μM) and low effect towards STAT1 5.

BD750 is an effective immunosuppressant and a JAK3 STAT5 inhibitor, inhibits IL-2-induced JAK3 STAT5-dependent T cell proliferation(IC50 of 1.5 μM and 1.1 μM in mouse and human T cells, respectively)

Homoharringtonine (HHT) is a natural alkaloid that inhibits the translation of proteins and is cytotoxic. Homoharringtonine acts on the ribosomes of tumor cells to inhibit the elongation step of protein translation, thereby inhibiting protein synthesis, and has antitumor activity.

Niclosamide (Niclocide)(BAY2353) is used to treat most tapeworm infections by inhibiting DNA replication.

Colivelin is a neuroprotective peptide and activator of STAT3. Colivelin is a hybrid peptide synthesized to enhance the neuroprotective effects of humanin (HN).

Pimozide (R6238) is a diphenylbutylpiperidine derivative and a dopamine antagonist with the antipsychotic property. Pimozide selectively inhibits type 2 dopaminergic receptors in the central nervous system (CNS), thereby decreasing dopamine neurotransmission and reducing the occurrence of the motor and vocal tics and delusions of parasitosis. In addition, this agent antagonizes alpha-adrenergic and 5-HT2 receptors.

Napabucasin (BBI608) is an orally available Stat3 and Y cell stemness inhibitor.