P450’s in drug discovery
Key human P450 isoforms involved in drug metabolism.
Of all the members of the family of human P450s, six isoforms (CYP3A4, CYP2D6, CYP2C8, CYP2C9, CYP2C19 and CYP1A2) participate in more than 95% of the metabolism of clinically used drugs and contribute to the metabolism of a huge number of xenobiotic chemicals. Thus, the tremendous interest shown by the pharmaceutical industry and the scientific community in the understanding and exploitation of these important enzymes has prompted vast investment of resources.
There are a large number of P450-related withdrawals of drugs that have caused huge losses to the pharmaceutical industry: examples are given below:
| Drug | Use | P450 involved | Effect of interaction |
| Terfenadine | Antihistamine | CYP3A4 | Fatal arrhythmias |
| Cisapride | Heartburn | CYP3A4 | Fatal arrhythmias |
| Cerivastatin | Lipid lowering drug | CYP2C8 | Rhabdomyolysis (muscle breakdown) |
| Astemizole | Antihistamine | CYP3A4 | Fatal arrhythmias |
| Mibefradil | Hypertension and angina | CYP3A4 | Fatal arrhythmias |
| Perhexiline | Angina | CYP2D6 | Nerve toxicity |
| Nefazodone | Antidepressant | CYP3A4 | Liver toxicity |
| Grepafloxacin | Antibiotic | CYP3A4 | Fatal arrhythmias |
