Conolidine: Re-engineering Molecules Used in Traditional Chinese Medicine

Researchers have demonstrated new abilities of Conolidine. Conolidine is a natural painkiller derived from the pinwheel flower and traditionally used in Chinese medicine, interacts with the newly identified opioid receptor ACKR3/CXCR7. The receptor  regulates opioid peptides naturally produced in the brain.

The researchers are from the Luxembourg Institute of Health (LIH) and Center for Drug Discovery at RTI International (RTI). 

Opioid peptides are small proteins that mediate pain relief and emotions by interacting with four molecular switches in the brain. The emotions include euphoria, anxiety, stress and depression.

ACKR3 functions as a “scavenger” that ‘traps’ the secreted opioids and prevents them from binding to the classical receptors, thereby dampening their analgesic activity and acting as a regulator of the opioid system.

They engineered  a form of conolidine, RTI-5152-12, which displays greater activity on the receptor. The researchers identified ACKR3 as the most responsive target for conolidine. This means the engineered molecule would perform better as painkillers. As they would tackle the effect of ACKR3 on opioid peptides secreted by the brain.

The researchers filed a joint patent in December 2020. More info.