ZG016 (Zelgen)

ZG016 is a preclinical small molecule inhibitor developed by Suzhou Zelgen Biopharmaceuticals, specifically targeting Ubiquitin-specific peptidase 1 (USP1). USP1 is a deubiquitinating enzyme that plays a vital role in the regulation of DNA damage repair pathways, particularly the Fanconi Anemia (FA) pathway and translesion synthesis (TLS). By inhibiting USP1, ZG016 prevents the deubiquitination of key substrates such as FANCD2 and PCNA, leading to the accumulation of DNA damage, increased genomic instability, and subsequent apoptosis. This mechanism is particularly effective in tumors with homologous recombination deficiency (HRD), such as those harboring BRCA mutations. ZG016 is being investigated for its potential as a monotherapy or in combination with PARP inhibitors to treat various solid tumors and overcome resistance to existing DNA-damaging therapies.