Discovering new painkillers

Familiar painkillers, or analgesics, such as paracetamol and aspirin, are not always effective in managing peoples pain, while stronger painkillers, such as morphine, can be highly addictive and can produce unwanted side effects.

 

The IMB Centre for Pain Research (CPR) is looking at animal venoms—such as those found in centipedes, spiders and cone snails—to develop new and more effective painkilling drugs. CPR uses a broad and comprehensive panel of assays for pain targets, addressing aspects of pain initiation and transmission using state-of-the-art screening technologies.

Pinpointing pain targets

Researchers are investigating how pain targets behave within pain pathways, right down to the molecular level, so they can work to improve the effectiveness of painkilling drugs, as well as prevent addiction and the unpleasant side effects associated with current drugs.

Using advanced NMR and X-ray crystallographic approaches, scientists can obtain accurate three-dimensional structure of molecules and precisely position the residues contributing to affinity. This knowledge will be used to improve target specificity, and, in parallel, will engineer out off-target liabilities to improve the therapeutic window of drug leads.

Mapping pain pathways

How the body feels pain is still not well understood. At the CPR, our research maps the complex pain pathways within our body. This will help us to better understand what can cause chronic pain. It will also help us to uncover new pain pathways in the body that could be targeted by painkillers.

Testing potential new treatments

CPR assesses the effectiveness of newly discovered compounds in the pain pathway of experimental models. Information gathered through this approach helps identify preferred compounds/candidate molecules, suitable patient populations, dosing routes, as well as strategies to minimise side effects in people living with pain.

Drug development

Molecules or drug targets that prove to be effective in managing pain in the lab will be chemically modified to be suitable for manufacturing. Researchers work to maximise storage and enzyme stability, ease of synthesis, and plasma half-life in vivo, without compromising therapeutic index, efficacy or safety.