PL37

PL37 (also known as Debio-0827) is an orally active small molecule dual enkephalinase inhibitor (DENKI) developed by the French biotechnology company Pharmaleads. The drug works by simultaneously inhibiting two key enkephalin-degrading enzymes: aminopeptidase N (APN) and neprilysin (NEP, also known as neutral endopeptidase). By protecting endogenous enkephalins from degradation, PL37 increases local enkephalin concentrations, which then activate peripheral μ-opioid receptors to provide pain relief without the central nervous system side effects typically associated with traditional exogenous opioids. PL37 has been evaluated in Phase IIa clinical trials for peripheral neuropathic pain of diabetic origin (painful diabetic neuropathy) and is also being investigated for the acute treatment of episodic migraine headache.