生化机理 |
Description: IC50 Value: N/A GS-9620 is a potent and selective orally active small molecule agonist of Toll-like receptor 7(TLR-7) in chimpanzees with chronic HBV infection [1]. GS-9620 is a novel oral agonist of Toll-like receptor 7 (TLR7) in development for the treatment of chronic viral hepatitis. TLR7 is a highly conserved innate immune receptor expressed primarily on plasmacytoid dendritic cells and B lymphocytes [2]. in vitro: N/A in vivo: Short-term oral administration of GS-9620 provided long-term suppression of serum and liver HBV DNA. The mean maximum reduction of viral DNA was 2.2 logs, which occurred within 1 week of the end of GS-9620 administration; reductions of >1 log persisted for months. Serum levels of HBV surface antigen and HBV e antigen, and numbers of HBV antigen-positive hepatocytes, were reduced as hepatocyte apoptosis increased. GS-9620 administration induced production of interferon-α and other cytokines and chemokines, and activated interferon-stimulated genes, natural killer cells, and lymphocyte subsets [1]. Induction of chemokines/cytokines and IFN-stimulated genes were seen at GS-9620 doses ≥2 mg, well below doses that induced serum IFN-α or led to clinical adverse events [2]. Clinical trial: A Study Evaluating GS-9620 in Treatment Naive Subjects With Chronic Hepatitis B. Phage1 |