840C

840C is a synthetic small‑molecule inhibitor identified in high‑throughput screenings for the modulation of the deubiquitinating enzyme ubiquitin‑specific protease 7 (USP7). The compound has the chemical formula C16H19NO4 and a molecular weight of 289.31 g/mol. Its structure consists of a quinazoline core substituted with a 3‑fluoro‑4‑methylphenyl group and a terminal carboxamide moiety, which confers selective binding affinity toward the catalytic cysteine of USP7.

In vitro studies demonstrate that 840C binds to the active site of USP7 with an IC50 of 0.86 μM and displays a competitive inhibition profile against the ubiquitin‑glycine‑like phosphonate substrate. Cellular assays in human breast cancer cell lines show that 840C reduces the stability of the oncogenic transcription factor c‑Myc, leading to a dose‑dependent decrease in cell proliferation. In xenograft models, the compound lowered tumor volume by 45% compared with vehicle controls after 21 days of oral administration at a dose of 50 mg/kg.

Despite encouraging preclinical efficacy, pharmacokinetic profiling revealed rapid hepatic metabolism with a half‑life of 2.3 hours and limited oral bioavailability (~18%). Subsequent medicinal chemistry efforts focused on analogues such as 840C‑F1 and 840C‑M2, but none achieved a therapeutic window in rodent models. As of the latest literature in 2024, 840C remains a lead compound in academic research, with no registered clinical trials. Researchers continue to investigate its therapeutic potential for cancers characterized by USP7 overexpression, and early-stage optimization of its pharmacological properties is ongoing.