A patent review of CYP3A4 inhibitors (2018 - present)

Cytochrome P450 3A4 (CYP3A4), one of the most important xenobiotic-metabolizing enzymes, plays a central role in drug metabolism and acts as a key mediator in drug-drug interactions. CYP3A4 inhibitors can potentiate the in vivo therapeutic effects of CYP3A4-substrate drugs via enhancing their systematic exposure levels. Two CYP3A4 inhibitors (ritonavir and cobicistat) have already been approved for modulating the exposure levels of CYP3A4-substrate drugs.

This review summarizes the newly patented CYP3A4 inhibitors in the period (2018-2024) by using the keywords 'CYP3A4' and 'inhibitor' in Espacenet database from academic institutions and industrial companies. The chemical structures and inhibition profiles of the patented CYP3A4 inhibitors, including the anti-CYP3A4 potency, inhibitory mechanisms, and other relevant information, are summarized and discussed.

Although diverse CYP3A4 inhibitors have been developed in the past few years, the development of more efficacious CYP3A4 inhibitors with favorable pharmacokinetic and safety profiles is still challenging. To maximize the benefit of CYP3A4 inhibitors, combination strategies should be used for the development of highly specific CYP3A4 inhibitors or degraders with efficacious anti-CYP3A4 effects and favorable pharmacokinetic profiles. Meanwhile, more efforts should be made to address the organ-targeting or tumor-targeting ability of CYP3A4 inhibitors for specific purposes.