Developing H3 relaxin analogs to treat pain

Patients suffering from moderate to severe and chronic pain are routinely prescribed opioid-related analgesics. When higher doses are needed, a patient can experience side effects such as constipation, sedation, and even respiratory failure and accidental death. Therefore, there’s an unmet medical and public health need for new analgesics to manage pain that can supplement or replace current opioid and non-opioid drugs.

We earlier hypothesised that the human relaxin-3 (H3 relaxin) peptide that targets the G-protein-coupled receptor, RXFP3, in the brain, could be the basis of a new treatment for pain relief. However, H3 relaxin is an insulin-like peptide with two (A and B) chains and three disulfide bridges. This complex structure means the native peptide is less suitable as a potential drug for targeting brain receptors via peripheral delivery.


  • Validate RXFP3 as a therapeutic target in the brain.

We’ve developed and patented a non-covalent stapling strategy to stabilise peptides and successfully used this strategy to create an α-helical B-chain mimetic of H3 relaxin. Our comprehensive dataset (in vitro and in vivo) confirms that the new B-chain mimetic, πH3B, is remarkably stable in serum and fully mimics the biological actions of the two-chain peptide, H3 relaxin.

Developing this stabilised peptidomimetic of H3 relaxin has uniquely positioned us to validate RXFP3 as a therapeutic target in the brain. This project will utilise our multidisciplinary expertise to chemically modify πH3B so that resulting analogue(s) can be delivered peripherally. Lead analogue(s) will be tested in clinically relevant pain models in mice to assess the relative effectiveness of different routes of administration (intraperitoneal, intravenous, or intranasal).

Research team


  • Professor Andrew Gundlach – Supervisor

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