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 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.

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.

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.

HODHBt is a STAT5-SUMO protein-protein interaction 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.

Artesunate (WR-256283) is part of the artemisinin group of drugs that treat malaria. It is a semi-synthetic derivative of artemisinin that is water-soluble and may therefore be given by injection. It is on the World Health Organization's List of Essential Medicines.

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.

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

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

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

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

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.

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.

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

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.

KT-333 is a potent, highly selective, heterobifunctional small molecule degrader of STAT3 for the treatment of a variety of STAT3-dependent pathologies, including hematologic malignancies and solid tumors.KT-333 specifically binds to STAT3 proteins at one end of the spectrum, and binds to the E3 ubiquitin ligase, VHL, at the other end.

AS1517499 is a potent STAT6 inhibitor with IC50 of 21 nM

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

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.

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.

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

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.

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.

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

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

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

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.

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.

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

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

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.

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.

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.

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.

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

Tetramethylcurcumin is a novel curcumin analog, is an effective inhibitors of STAT3 phosphorylation, DNA binding activity, and transactivation in vitro.it also inhibits colony formation in soft agar, cell invasion, and exhibit synergy with the anti-cancer drug doxorubicin against breast cancer cells.

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.

Ochromycinone (STA 21) is a selective STAT3 inhibitor.

Stafia-1 is a potent STAT5a inhibitor (IC50=22.2 μM), displaying high selectivity over STAT5b and other STAT family members.

CASIN (Pirl1-related Compound 2) is a specific inhibitor of GTPase Cdc42 (IC50: 2 uM).

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.

Garcinone C is a xanthone derivative extracted from Garcinia oblongifolia Champ with anti-inflammatory, astringency, and granulation-promoting activities. Garcinone C is an AChE inhibitor and has potential cytotoxic effects on certain cancers.

BP-1-102 is an orally active, effective, and specific STAT3 inhibitor that binds Stat3 (Kd: 504 nM), blocks Stat3-phosphotyrosine (pTyr) peptide interactions and Stat3 activation (4-6.8 μM), and selectively inhibits the 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].