CYP3A4 is the most clinically relevant drug metabolizing enzyme in the body, as it is responsible for the oxidation and breakdown of ~60% of current drugs on the market. Researchers at UCI have developed novel CYP3A4 inhibitors, that are highly potent and more specific, exhibit fewer side effects, and are both cheaper, and easier to-synthesize than current commercially available CYP3A4 inhibitors.
Inhibition of CYP3A4 has proven to be efficacious in
prolonging the overall therapeutic effectiveness of a number of drugs, reducing
repeated dosing and lowering costs. Current commercially available CYP3A4
inhibitors are used as pharmacoenhancers, but lack potency and are prone to
causing serious side effects in both the liver and adrenal glands. As such, their
utility is limited. In order to safely
enhance the effectiveness of wider range of pharmaceutical treatments, there is
a dire need for a class of CYP3A4 inhibitors with increased potency that are
also non-toxic at therapeutic doses.
UCI researchers have used rational structure-based design to synthesize and characterize two new classes of CYP3A4 inhibitors with superior binding affinity and inhibitory potency. Furthermore, the demonstrated ease of production and reduced synthesis costs of these novel compounds provide commercial scalability advantages over current CYP3A4 inhibitors.
As a pharmacoenhancer or booster for otherwise quickly metabolized drugs for use in anti-HIV, anti-HCV, anti-cancer and immunosuppressive therapy
Currently the CYP3A4 inhibitor design is being further optimized to identify functional groups leading to the strongest binding and inhibition of CYP3A4. The most potent inhibitors will be tested for liver toxicity using human liver microsomes and in cell culture, then the less toxic compounds will be tested in vivo for off-target effects, pharmacokinetics, pharmacodynamics and pharmacoenhancing effects.