CYP3A4 inhibitors (SJ-24-0036) 

St. Jude Reference #SJ-24-0036

Description

Drug-drug interactions occur with use of multiple medications. Cytochrome P450 (CYP) 3A4 metabolizes a large portion of marketed drugs. To maintain the efficacy of drugs metabolized by CYP3A4, pan-CYP3A inhibitors such as ritonavir are often co-administered. Although selective CYP3A4 inhibitors have greater therapeutic benefits as they avoid inhibiting unintended CYPs and undesirable clinical consequences, the high homology between CYP3A4 and CYP3A5 has hampered the development of such selective inhibitors. 

Researchers at St. Jude report a series of selective CYP3A4 inhibitors with scaffolds identified by high-throughput screening. Structural, functional, and computational analyses revealed factors that disfavor the binding of selective CYP3A4 inhibitors to CYP3A5 and demonstrate the feasibility to selectively inhibit CYP3A4 and provide guidance for designing better CYP3A4 selective inhibitors as drug candidates. These can also be used as co-drugs to maintain the efficacy of drugs that are metabolized by CYP3A4.

Keywords

Drug interaction, Cytochrome P450 (CYP) 3A4, CYP3A4, pan-CYP3A inhibitor, ritonavir, CYP3A5, co-drug

Granted patents or published applications

Pending

Related scientific references

Wang, J., Nithianantham, S., Chai, S.C. et al. Decoding the selective chemical modulation of CYP3A4. Nat Commun 16, 3423 (2025). https://doi.org/10.1038/s41467-025-58749-8

Licensing opportunities

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