Anti-Human ADCYAP1R1 Monoclonal Antibody (Zelminemab)

ADCYAP1R1, also known as the PAC1 receptor (pituitary adenylate cyclase-activating polypeptide type 1 receptor), is a class B G protein-coupled receptor predominantly expressed in the central nervous system. It serves as the specific receptor for the neuropeptide PACAP, binding both active forms (PACAP27 and PACAP38) with significantly higher affinity than VIP. The protein features the classical structure of class B GPCRs, comprising a large extracellular N-terminal domain responsible for ligand recognition and seven transmembrane helices. Through complex alternative splicing, its gene generates multiple isoforms, with subtle differences in the intracellular loops determining their preferential coupling to distinct G proteins (such as Gs or Gq/11), thereby activating diverse downstream signaling pathways including cAMP-PKA, PLC-IP3/DAG, and MAPK/ERK, enabling fine-tuned functional regulation. Physiologically, ADCYAP1R1 serves as a core regulatory hub in neuroendocrine and stress responses, participating in the regulation of various hormone releases (e.g., adrenocorticotropic hormone, catecholamines), fear memory consolidation, circadian rhythm synchronization, as well as insulin secretion and gastrointestinal function. Pathologically, polymorphisms in this gene (such as rs2267735) have been significantly associated with the risk of post-traumatic stress disorder (PTSD) in females, while dysregulation of its mediated signaling pathways is also recognized as a key pathological mechanism in chronic pain and migraine, making it an emerging important therapeutic target for migraine drug development.