Brain tumors with the H3 K27M mutation are among the most aggressive, primarily affecting children and young adults. These tumors grow rapidly and are resistant to conventional treatments. Chimerix is developing ONC201, a targeted therapy designed to combat these tumors at the molecular level.
ONC201 is an oral small molecule drug and the first in a new class of compounds called imipridones (generic name: dordaviprone). It works by targeting two key cellular components:
- Dopamine receptor DRD2: This receptor regulates the Ras signaling pathway, which controls cell proliferation. ONC201 inhibits DRD2, helping to slow tumor growth.
- ClpP protease in mitochondria: ONC201 activates ClpP, leading to increased degradation of mitochondrial proteins essential for energy production. This energy disruption triggers stress in cancer cells, leading to selective tumor cell death.
Clinical studies show ONC201 is well tolerated and capable of shrinking H3 K27M-mutant brain tumors. This unique mechanism of action makes it a promising candidate for patients in urgent need of effective treatment.
Learn more at chimerix.com
