GLP-26

GLP-26 is a novel small‑molecule glyoxamide derivative that functions as a hepatitis B virus (HBV) capsid assembly modulator, altering nucleocapsid assembly to prevent viral DNA replication and reduce cccDNA amplification and HBV e antigen (HBeAg) and surface antigen (HBsAg) levels in vitro and in HBV-infected humanized mouse models.[1][2] It binds the HBV core protein with higher affinity than earlier capsid modulators such as GLS4, stabilizing formation of tight, intact capsids and exhibiting single‑digit nanomolar antiviral activity without significant mitochondrial toxicity.[1] In preclinical mouse and cynomolgus monkey studies, GLP-26 shows favorable oral bioavailability, multi-species plasma and microsomal stability, high plasma protein binding, and a benign cardiac safety profile in primary human cardiomyocytes, and demonstrates synergistic antiviral effects when combined with the nucleoside analog entecavir.[1][2]