It is challenging to find a way to precisely target a drug by using a small molecule that conforms to its target precisely and yet still allows the drug to move across a cellular membrane and interact with a specific cell type. Traditionally, drugs have focused on molecules that are small and have rigid, nonpolar chemical structures. Many small molecules are difficult to selectively target because they are unable to bind to specific targets. However, large molecules that are linked to a variety of targets can be used to create novel drugs.
UCSF researchers Kevin Lou, an MD-PhD student, Luke Gilbert, PhD, and Kevan Shokat, PhD, report on a molecular pathway that allows larger molecules to be transported to cells. Large, complex drugs bind differently to different targets, are effectively absorbed by the target cells, and can be harnessed to create new drugs for the treatment of cancer and other diseases.
Using a complex combination combining functional genomics and chemical methods, the researchers discovered that IFITM proteins are required for regulating cell growth and allowing drugs to function efficiently. These are a family of proteins that are found in many cell membranes, and they are key in allowing cells to resist many pathogens.
Most drugs are small molecules that behave simply because they are simple to design and have simple rules governing the number of small sticky groups on their surfaces. Many important drug targets, such as kinases involved in cancer, are difficult to selectively target with existing drugs.