Axelopran is an oral PAMORA which is under development by Theravane Biopharma. It has completed phase II in clinical trials in more than 400 patients with OIC. Axelopran has a different chemical structure from other PAMORAs but with a similar mechanism of action. It acts as an antagonist for MOR, KOR and DOR, but with higher affinity for MOR and KOR than for DOR. Like other PAMORAs, the main goal is the treatment of OIC.
Axelopran is also being investigated in fixed-dose combination (FDC) with oxycodone. It is done by using spray coating technology to create an FDC of axelopran and controlled-release oxycodone.
There is a demand for optimization of the receptor selectivity and affinity accompanied by an exploration of candidate compounds regarding their route of administration. These are the main objectives and future strategies for drug discovery and the development of PAMORAs.
Predominantly, the MORs exhibit functionally selective agonism. Therefore, future possible candidate compounds that target OIC are PAMORAs with optimized selectivity and affinity.