STAT

Balsalazide sodium hydrate (Balsalazide disodium) is an anti-inflammatory compound used in the treatment of Inflammatory Bowel Disease.Balsalazide sodium hydrate is a new 5-aminosalicylic acid (5-ASA) containing prodrug. High dose Balsalazide sodium hydrate(3.0 g twice daily) was superior in maintaining remission in patients with ulcerative colitis compared with a low dose (1.5 g twice daily) or a standard dose of mesalazine (0.5 g three times daily). All three treatments were safe and well tolerated [1]. Balsalazide sodium hydrate is approved for the treatment of mild-to-moderate active UC. It is efficacious for the induction of remission in mild to moderate UC and has a favorable safety profile, with the added advantages of greater efficacy of remission induction and rapidity of onset [2].

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.

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.

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.

AS2863619 is an oral inhibitor of cyclin-dependent kinase 8 (CDK8) and CDK19. Inhibition of CDK8 19 can enhance the activation of STAT5, thereby activating the Foxp3 gene. It can convert antigen-specific effector memory T cells into Foxp3+ regulatory T cells to study various immune diseases.

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.

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.

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.

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

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

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

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.

Solamargine (δ-Solanigrine) is a major steroidal alkaloid glycoside extracted from a traditional Chinese medicine herb, Solanum nigrum L. (SNL); has been shown to inhibit growth and induce apoptosis of various cancer cells.

Angoline (6-Methoxyldihydrochelerythrine) hydrochloride is a potent and selective IL6/STAT3 signaling pathway inhibitor(IC50 : 11.56 μM). It inhibits STAT3 phosphorylation and its target gene expression, and inhibits cancer cell proliferation.

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.

SC-43 is a potent and orally active agonist of SHP-1 (PTPN6). SC-43 inhibits the phosphorylation of STAT3 and induces cell apoptosis, and with anti-fibrotic and anticancer effects.

NT219 is a dual inhibitor of insulin receptor substrate 1/2 (IRS1/2) and STAT3, enhances the aggregation of misfolded prion protein NT219 affects the levels of certain molecular chaperones and inhibits STAT3 phosphorylation NT219 is useful for the study of cancer and neurodegenerative diseases.

HODHBt is a STAT5-SUMO protein-protein interaction inhibitor.

Eriocalyxin B induces apoptosis and cell cycle arrest in pancreatic adenocarcinoma cells through caspase- and p53-dependent pathways, should be considered a candidate for pancreatic cancer treatment; it is a specific inhibitor of STAT3, it directly target

AS1810722, a fused bicyclic pyrimidine derivative, is an orally active and potent inhibitor of STAT6, demonstrating an IC50 of 1.9 nM. It exhibits effective inhibition of CYP3A4, positioning it as a promising candidate for research into allergic diseases, including asthma and atopic conditions.

Saikosaponin D is a novel SERCA inhibitor by inhibiting NF-κB and STAT3 signaling to protect against acetaminophen-induced hepatotoxicity.

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

AS1517499 is a potent STAT6 inhibitor with IC50 of 21 nM

SH-4-54 is a most potent, small molecule, nonphosphorylated STAT3 inhibitor.

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

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

SD-36 TFA is a selective and highly efficient STAT3 degrader with a Kd value of about 50 nM.SD-36 has anticancer and antitumor activity, and can break down mutant STAT3 proteins in cells and inhibit STAT3 transcription.SD-36 promotes growth inhibition and induces apoptosis through inhibition of Mcl-1 in gliomas.

Jolkinolide B is a bioactive diterpene isolated from the roots of Euphorbia fischeriana Steud. Jolkinolide B induces apoptosis in cancer cells. Jolkinolide B can be used for studies on preventing and treating osteolysis.

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.

1. Casticin (Vitexicarpin) can significantly reduce vascular inflammation, through inhibition of ROS-NF-κB pathway in vascular endothelial cells. 2. Casticin may become a potential leading drug in the therapy of prostate carcinoma.

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

Ponicidin (Rubescensine B) is a diterpenoid derived from Rabdosia rubescens that exhibits immunoregulatory, anti-inflammatory, anti-viral, and anti-cancer activity. Ponicidin induces apoptosis of gastric carcinoma cells, decreases the phosphorylation of JAK2 and STAT3, and shows no effect on the protein levels of JAK2 and STAT3.

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

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.

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

Kurarinone is a flavonoid extracted from the shrub Sophora flavescens, which has anti-tumor, estrogenic and anti-inflammatory activities, and also has a strong inhibitory effect on immune responses.

Sophocarpine, a major ingredient of Sophora alopecuroides, has a wide range of pharmacological effects.

(R)-Lisofylline ((R)-Lisophylline) is an inhibitor of lysophosphatidic acid acyltransferase (IC50 = 0.6 µM) that interrupts IL-12 signaling-mediated STAT4 activation, making it useful for studies on the treatment of type 1 diabetes and autoimmune disorders.

ML115 is a potent and selective activator of transcription 3 (STAT3), with abn EC50 of 2.0 nM, and is inactive against the related STAT1 and NFκB anti-targets.

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

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

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.

Alantolactone is a selective inhibitor of STAT3 that induces cancer-associated apoptosis and has antitumor activity.

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.

IST5-002 (N6-Benzyladenosine-5'-phosphate) is a selective Stat5a b inhibitor with anticancer activity that inhibits the transcriptional activity of Stat5a b and induces apoptosis and death of prostate cancer cells and chronic myelogenous leukemia (CML) cells, which can be used for cancer research.

Ochromycinone (STA 21) is a selective STAT3 inhibitor.

2-NP is a STAT1 enhancer.

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.