Research Team Makes Progress in Creating Oral Medication for Some Cancers and Alzheimer's

A research team has presented findings that detail a new strategy for drug delivery called “chemical endocytic medicinal chemistry,” which could make certain complex and large-molecule drugs for hard-to-treat diseases available orally.

The strategy involves using “the body’s own protein receptors found on the surface of many cells called CD36 to help large and water-soluble ‘polar’ drugs enter cells more efficiently. [The researchers] demonstrated how chemically optimizing interactions with CD36 allows drugs previously thought too large to be absorbed by cells.”

Molecules larger than 500 Daltons (Da) “were believed to be practically unusable due to the challenges of cell access and bioavailability,” which “greatly restricted the kinds of compounds that could be developed as induced proximity drugs.” Induced proximity is a process by which “molecules bring proteins together to create a desired interaction and/or chemical reaction.”

This new discovery bypasses that limitation by “chemically enhancing CD36-mediated uptake, amplifying the efficiency of larger and polar molecules to enter target cells.” The key experimental results validating that discovery were “independently reproduced by each of the teams involved in the study.”

The new process “represents a paradigm shift that removes…challenges by using the membrane receptor-mediated cellular entry.” There are also likely additional cell receptors beyond CD36 that “could be targeted for chemical endocytosis.” This opens up new avenues in drug development.