Mu-opioid receptor-Kappa-opioid receptor heteromer (HM2K) (HM2K)

The HM2K opioid receptor complex is a G protein-coupled receptor (GPCR) heteromer formed by the physical interaction of the Mu-opioid receptor (MOR) and the Kappa-opioid receptor (KOR) [2, 3]. This complex represents a novel therapeutic target designed to address the limitations of traditional opioid analgesics, which primarily target monomeric MOR and are associated with high risks of addiction and respiratory depression [1, 3]. By selectively activating the HM2K heteromer, therapeutic agents can induce potent analgesia while potentially avoiding the recruitment of pathways responsible for tolerance and dependence [2]. This unique pharmacological profile is achieved through receptor-interactomics, where the interaction between the two receptors creates a distinct signaling entity with its own functional properties [3]. The lead candidate targeting this complex, BLUE-181, is being developed for the treatment of chronic pain, irritable bowel syndrome (IBS), and anxiety disorders [1, 4]. Research suggests that targeting such heteromers allows for improved tissue and disease selectivity, minimizing side effects seen with non-selective opioid agonists [2, 3].

Other names

MOR-KOR heteromerMu-Kappa opioid receptor complexHeteroMer-Mu-KappaHM2K receptor

Selective activation of the Mu-opioid receptor-Kappa-opioid receptor heteromer