A patent review on the development of human cytochrome P450 inhibitors

Abstract

Granted patents, albeit mostly embodying evidence from in vitro and limited preclinical trials, demonstrate good potential for use in industry and the clinic following future human trials. Indeed, only a handful is on the market or under clinical evaluation. Diagnostic monoclonal antibodies (mAbs) show high specificity for CYP families 1, 2, and 3, while potent inhibitors of CYPs 17, 19, 24, 26, 3A4 activities, in use with or without other drugs, display potential in treating prostate and breast cancers, dermatology, and improved retroviral therapy, although some may have challenges in delivery to target tissues. The involvement of this superfamily of enzymes in cellular functions, a multitude of disease states, and pharmacogenetics make them ideal candidates to better understand contemporary human health issues and identification of targeted, specific, and potent inhibitors is a useful strategy to employ, toward achieving that wider goal.

Variability in bioavailability of small molecular tyrosine kinase inhibitors

“…Concomitant use of an inducer or inhibitor of these proteins can significantly affect the absorbed dose of substrate smTKIs, ingestion of grapefruit juice is such an example [115][116][117]. An increasing list of inducers and inhibitors can be found in literature [114,118]. Another variable is genetic polymorphism.…”

The Pharmacology of the Cytochrome P450 Epoxygenase/Soluble Epoxide Hydrolase Axis in the Vasculature and Cardiovascular Disease

“…However, the majority of work published to date has focused on the consequences of P450 inhibition on the bioavailability of anticancer agents, such as tamoxifen (Coller, 2003;Stearns et al, 2003), rather than determining the consequences of P450 inhibition per se. Certainly, a large number of P450 inhibitors already exist or are being developed (Francis and Delgoda, 2014). However, given that P450 enzymes metabolize xenobiotics (e.g., nifedipine, 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, and warfarin), targeting the proximal part of the pathway may lead to unwanted complications and side effects in patients receiving other medications.…”

Treatment of Rats with Apocynin Has Considerable Inhibitory Effects on Arylamine N-Acetyltransferase Activity in the Liver

“…Many natural organic compounds are known to display a valuable potential for cancer-prevention in chemically induced carcinogenesis models 15 16 17 . Tumour-preventive strategies may include the use of phytochemicals for either their antioxidant properties which allow the modulation of the intracellular redox status finally leading to the apoptosis of tumour cells, or their inhibitory potency towards some metabolic pathways which activate procarcinogens 18 .…”