Drug Targets

Elizabeth Dallman, Pharm.D. Candidate; Caitlin Munro, Pharm.D. Candidate; Emily Loudermilk, Pharm.D. Candidate.

Drug Targets - Receptors

A receptor is a structure that accepts and binds to certain substances in the body and is usually located on the surface of the cell. Many kinds of receptors exist including those that sense pain, mediate production of cholesterol, and control allergic symptoms. Receptors bind with specific molecules that indicate a specific reaction in the body is to take place.

For instance, consider the "typical" allergic reaction. A person is exposed to a substance (e.g. pollen) which results in the release of histamine (H) into the blood. Histamine interacts with histamine receptors (HR) which results in the symptoms of an allergy, such as a "runny nose", or "itchy eyes". The individual can choose to take an antihistamine (A) drug to treat the allergic response. The figure below depicts how a drug (here, the antihistamine) interacts with the histamine receptor (HR), a drug target, to keep histamine (H) from interacting with the receptor, thus blocking histamine from causing the allergic symptoms.

Drug Targets - Transporters

Because of the structure of the cell membrane it can be difficult for most substances to make it across the membrane into the cell to participate in cellular processes. Transporter proteins embedded in the membrane can help these substances cross the membrane into the cell, and can speed up the rate in which molecules normally make it into the cell. These proteins usually bind to one substance at a time and once attached, change their shape to allow the substance passage into the cell.

As an example, some drugs used to treat the blood cancer leukemia are transported into the cell by transporters called nucleoside transporters. These drugs work inside the cell, so the transporters are important in that they allow the drugs to get into the cancer cells and stop them from growing.

The image at the right shows how the transporter (T; a drug target) takes the drug (D) from outside the cell to inside the cell. Some drug transporters move drug from inside the cell to outside the cell. If we use the example from above, if drug is moved out of a cell by a transporter, it cannot work inside the cell. In this case, the cancer cell would not be killed. This is one way cancer cells can be resistant to the effects of a drug. Genetics can influence the activity of drug transporters.

Drug Targets - Enzymes

Enzymes are protein chemicals that work inside and outside of cells to speed up existing reactions. These reactions vary in their function with some enzymes playing an important role in "breaking down" drugs. These drug metabolizing enzymes are what "remove" drug from the body. The image below shows a drug (substrate) being metabolized by an enzyme. The drug (substrate) "fits" into the enzyme like a "key and lock". The enzyme changes the chemical structure of the drug to form products (metabolites), which are not the original drug. Genetics can influence the activity of drug metabolizing enzymes.

Sources of Information

Cox, AG. Pharmacogenomics and Drug Transport/Efflux. American Society of Health-System Pharmacists. URL:http://www.ashp.org/DocLibrary/Bookstore/P2340-Sample-Chapter.aspx. Accessed: 2012-10-09.

Moroney, AC. Drug-Receptor Interactions. The Merck Manual. 2007. URL:http://www.merckmanuals.com/professional/clinical_pharmacology/pharmacodynamics/drug-receptor_interactions.html. Accessed: 2012-10-09.

Sadava D, Hillis DM, Heller HC, and Berenbaum MR. Life: The Science of Biology. 9th ed. Sunderland, MA: W. H. Freeman and Company; 2011.