ifn-a-14

DU-14 (PTP1B TC-PTPPROTAC) 是一种高效且具选择性的PTP1B和TC-PTP双重PROTAC降解剂，对PTP1B和TC-PTP磷酸酶活性的 IC50分别为24.2 nM和30.1 nM。此化合物能够增强IFN-γ信号传导、促进T细胞活化，并具有抗肿瘤活性。

Benpyrine is a highly specific and orally active TNF-α inhibitor with a KD value of 82.1 μM. Benpyrine tightly binds to TNF-α and blocks its interaction with TNFR1, with an IC50 value of 0.109 μM. Benpyrine has the potential for TNF-α mediated inflammatory and autoimmune disease research[1]. Benpyrine (5-20 μM; 14 hours; RAW264.7 cells) pretreatment results in a dose-dependent decrease in the phosphorylation of IκBα in RAW264.7 cells (stimulated with 10 ng mL TNF-α or 1 μg mL LPS). Benpyrine abolishes the TNF-α-induced nuclear translocation of NF-κB p65 in RAW264.7 cells[1].Benpyrine only blocks cell death induced by TNF-αWT and Y119A, and increases the cell survival rate up to 80%. Benpyrine does not obviously affect L57A- and Y59L-induced cytotoxicity in L929 cells[1]. Benpyrine (25-50 mg kg; oral gavage; daily; for 2 weeks; Balb c mice) treatment significantly relieves the symptoms of collagen-induced arthritis. Benpyrine dose-dependently decreases the levels of proinflammatory cytokines, such as IFN-γ, IL-1β and IL-6, and increases the concentration of the anti-inflammatory cytokine IL-10[1].Endotoxemia murine model shows that Benpyrine (25 mg kg) could attenuate TNF-α-induced inflammation, thereby reducing liver and lung injury[1]. [1]. Weiguang Sun, et al. Discovery of an Orally Active Small Molecule TNF-α Inhibitor. J Med Chem. 2020 Jul 15.