GS-5801

GS-5801 is an investigational, liver-targeted small molecule prodrug developed by Gilead Sciences for the treatment of chronic hepatitis B (CHB). It is an ethyl ester prodrug of the active parent compound GS-080, engineered to improve cellular permeability, oral bioavailability, and liver accumulation. GS-5801 functions as an inhibitor of lysine demethylase 5 (KDM5), an epigenetic 'eraser' enzyme that demethylates di- and tri-methylated lysine 4 on histone 3 (H3K4me3). By inhibiting KDM5, GS-5801 causes the accumulation of H3K4me3 on chromatin, which suppresses the transcription of HBV RNA, DNA, and antigens. Although it was the first KDM5 inhibitor to reach clinical trials (Phase 1a and Phase 1b), its development was suspended due to a lack of antiviral efficacy observed in humanized mouse models and clinical studies, despite achieving predicted pharmacodynamic levels.

Other names

GS-080GS080GS 080