Cytochrome P450 enzymes (CYPs) are a heme-containing protein superfamily that metabolizes a wide variety of xenobiotics, including metabolic clearance of the vast majority of prescribed drugs, as well as foreign toxic chemicals to which the body is exposed.
Most drugs undergo deactivation by CYPs, either directly or by facilitated excretion from the body. Some substances are bioactivated by CYPs to form pharmacologically active compounds. CYP450 inhibition may lead to elevated in vivo plasma levels of a co-administered drug metabolized by the inhibited enzyme.
At Life Chemicals, we designed this Cytochrome Inhibitor Screening Library with a ligand-based approach to offer over 1,900 structurally diverse screening compounds capable of fitting the cytochrome binding site to form donor/acceptor bonds and result in CYP activity modification.
The compound selection can be customized based on your requirements, cherry picking is available.
Please, contact us at orders@lifechemicals.com for any additional information and price quotations.
Background information
Cytochrome P450 enzymes play a crucial role in the biosynthesis of prostaglandins and steroid hormones. CYPs facilitate various oxidative reactions, including hydroxylation, epoxidation, and reduction. They are versatile in their catalytic activity, acting on a wide range of substrates that span from simple alkanes to complex endogenous molecules like steroids, fatty acids, and drugs. Cytochrome P450s are critical in drug discovery due to two of the most significant problems in clinical pharmacology:
- metabolism-mediated drug-drug interactions (DDI)
- individual variability in drug metabolism.
There are eleven CYP families expressed in the human liver and gastrointestinal tract, and five of them (CYPs 1A2, 2C9, 2C19, 2D6, and 3A4) are involved in about 95 % of the known drug metabolism. The cytochrome family members can be characterized by a common site structure with rigid conformation due to the presence of a heme group.
Compound selection
First, a reference set of compounds with reported CYP inhibition was obtained from the ChEMBL database. Subsequently, we thoroughly analyzed the Life Chemicals HTS Compound Collection to identify close analogs of known cytochrome inhibitors. This analysis was based on a 2D fingerprint similarity search with a Tanimoto cut-off greater than 0.85, using MDL public key fingerprints. This allowed us to generate the screening set of more than 1,900 screening compounds that are potential binders (inhibitors or inducers) of the following Cytochrome P450 enzymes:
- Cytochrome P450 1A2
- Cytochrome P450 1A1
- Cytochrome P450 3A4
- Cytochrome P450 2D6
- Cytochrome P450 19A1
- Cytochrome P450 11B1
- Cytochrome P450 2C9
- Cytochrome P450 2B6
- Cytochrome P450 2A6
- Cytochrome P450 17A1
- Cytochrome P450 2C19
- Cytochrome P450 3A4/3A5
- Cytochrome P450 51
- Cytochrome P450 2C8
- Cytochrome P450 11B2
Representative screening compounds from the Cytochrome Inhibitor Screening Library
