STAT

Osunprotafib (ABBV-CLS-484) is a potent, orally bioavailable PTP1B/PTPN2 inhibitor in clinical trials for solid tumors. [1] Osunprotafib (ABBV-CLS-484) stimulates the tumor microenvironment and promotes natural killer cell and CD8 T cell function and enhances T cell anti-tumor immunity by enhancing JAK-STAT signaling and reducing T cell dysfunction. [2]

AK-1690 is a potent and selective STAT6 PROTAC degrader that induces degradation of STAT6 proteins in cells (DC50=1 nM) and depletes STAT6 proteins in mouse tissues, which can be used in cancer research.

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].

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.

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.

Ritlecitinib (PF-06651600) is an orally available, selective JAK3 inhibitor with an IC50 of 33.1 nM and does not affect the activity of JAK1/2.

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.

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

Astaxanthin (trans-Astaxanthin) is a keto-carotenoid in the terpenes class of chemical compounds. It is classified as a xanthophyll but it is a carotenoid with no vitamin A activity. It is present in most red-colored aquatic organisms. Astaxanthin has shown to mediate anti-oxidant and anti-inflammatory actions. It may be found in fish feed or some animal food as a color additive.

Atranorin shows significant antinociceptive and antiinflammatory activities, it has a relevant redox-active action, acting as a pro-oxidant or antioxidant agent depending on the radical, also, it will exert cytoprotective effects on cells under oxidative

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

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. 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

AS1517499 is a blood-brain barrier permeable inhibitor of STAT6 phosphorylation (IC50= 21 nM).

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.

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

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.

Anti-Mouse NK1.1 Antibody (PK136) is an IgG2a class antibody of murine origin targeting NK1.1, which eliminates NK1.1 and NK1.1NKT cells and inhibits NK1.1 signaling in peripheral blood, spleen, and lung tissues, and can be used in the study of heart and lung failure.

Butyzamide is an effective and oral Mpl activator. It is a novel non-peptide-based molecule with antagonistic effects on thrombopoietin (TPO) receptors, which promotes proliferation of human Mpl (hMpl) expression and mouse pro B cell line Ba/F3. The phosphorylation of JAK2, STAT3, STAT5 and MAPK is induced. Butyzamide has been shown to help increase platelet levels in mouse xenotransplantation trials.

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.

Flubendazole (Flumoxane) is available OTC in Europe that is an anthelmintic using to treat worm infection in humans.

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.

Glycochenodeoxycholic Acid (Lithocholylglycine) is a glycine conjugate of lithocholic acid, a bile acid. It is increased in livers of mice that are fed diets supplemented with ursadeoxycholic acid. Glycolithocholic acid levels are decreased in lean mice treated with obestatin. Serum glycolithocholic acid levels increase with age in children.

Delphinidin chloride, a natural plant pigment found in berries and red wine, is a precursor of certain anthocyanins. Delphinidin chloride induces the release of nitric oxide from the vascular endothelium, resulting in vascular relaxation. At the dose of 1-40 μM, epithelial growth factor receptor signaling and estrogen receptor α expression were inhibited, which was associated with apoptosis and autophagy. Delphinidin chloride regulates JAK/STAT3 and MAPKinase signaling. Delphinidin also inhibited the histone acetyltransferase activity of p300/CBP (IC50 was about 30 μM).