δ Opioid Receptor/DOR Activator

BMS-986187 is an δ-opioid receptor-selective positive allosteric modulator (PAM) with an EC₅₀ of 0.03 μM and a pK_B of 6.02 (～1 μM). BMS-986187 has no observable PAM activity at the μ-receptor (EC₅₀=3 μM).

RB 101 is a blood-brain barrier-crossing prodrug as well as aminopeptidase N and neutral endopeptidase-24.11 inhibitor. RB 101 blocks enkephalin breakdown, elevates extracellular enkephalin levels and activate δ-opioid receptor and dopamine D1 receptor. RB 101 can be used for the research of pain, depressive syndromes, and diabetic neuropathy.

PL37 (Debio-0827) is an orally active, blood-brain barrier permeable dual enkephalinase inhibitor. PL37 inhibits aminopeptidase N, neprilysin, and metalloproteases, thereby blocking the degradation of endogenous enkephalins, elevating enkephalin levels, and activating peripheral μ- and δ-opioid receptors. PL37 induces mitochondrial dysfunction, mitophagy, and apoptosis, inhibits endothelial cell proliferation, migration, invasion, and tube formation, and suppresses hemangioma tumor growth and angiogenesis. PL37 can be used in research related to peripheral neuropathic pain, osteosarcoma-induced hyperalgesia, painful diabetic neuropathy, migraine, bone cancer pain, neuroinflammatory pain, and infantile hemangioma.