The scientists, led by Loren Walensky, MD, PhD, have identified a prototype compound that “flips a switch” to directly activate one of the most powerful death proteins, known as BAX, triggering apoptosis, or self-destruction of unwanted cells.
“Having identified the ‘on switch’ for the BAX protein several years ago, we now have a small molecule that can directly turn this death protein on,” says Walensky, senior author of the report.
…The development exploited the discovery by Walensky’s team of a distinctive groove, or “trigger site,” on the BAX protein that converts it from a quiescent form to an active one. When activated, BAX damages the cell’s mitochondria, releasing signals that break the cell apart and digest its pieces. This process of programmed cell death is part of a natural check-and-balance mechanism to control cellular life and death…
“We find that small molecule targeting of the BAX trigger site is achievable and could lead to a new generation of apoptotic modulators that directly activate BCL-2 executioner proteins in cancer and other diseases driven by pathologic apoptotic blockades,” write the authors.