TY - JOUR
T1 - Orphan GPR52 as an Emerging Neurotherapeutic Target.
AU - Ali, Saghir
AU - Wang, Pingyuan
AU - Murphy, Ryan
AU - Allen, John
AU - Zhou, Jia
PY - 2024/2/20
Y1 - 2024/2/20
N2 - GPR52 is a highly conserved, brain-enriched, Gs/olf-coupled orphan G protein-coupled receptor (GPCR) that controls various cyclic AMP (cAMP)-dependent physiological and pathological processes. Stimulation of GPR52 activity might be beneficial for the treatment of schizophrenia, psychiatric disorders and other human neurological diseases, whereas inhibition of its activity might provide a potential therapeutic approach for Huntington’s disease. Excitingly, HTL0048149 (HTL’149), an orally available GPR52 agonist, has been advanced into phase I human clinical trials for the treatment of schizophrenia. In this concise review, we summarize the current understanding of GPR52 receptor distribution as well as its structure and functions, highlighting the recent advances in drug discovery efforts towards small-molecule GPR52 ligands. The opportunities and challenges presented by targeting GPR52 for novel therapeutics are also briefly discussed.
AB - GPR52 is a highly conserved, brain-enriched, Gs/olf-coupled orphan G protein-coupled receptor (GPCR) that controls various cyclic AMP (cAMP)-dependent physiological and pathological processes. Stimulation of GPR52 activity might be beneficial for the treatment of schizophrenia, psychiatric disorders and other human neurological diseases, whereas inhibition of its activity might provide a potential therapeutic approach for Huntington’s disease. Excitingly, HTL0048149 (HTL’149), an orally available GPR52 agonist, has been advanced into phase I human clinical trials for the treatment of schizophrenia. In this concise review, we summarize the current understanding of GPR52 receptor distribution as well as its structure and functions, highlighting the recent advances in drug discovery efforts towards small-molecule GPR52 ligands. The opportunities and challenges presented by targeting GPR52 for novel therapeutics are also briefly discussed.
U2 - 10.1016/j.drudis.2024.103922
DO - 10.1016/j.drudis.2024.103922
M3 - Article
C2 - 38387741
SN - 1359-6446
VL - 29
JO - Drug Discovery Today
JF - Drug Discovery Today
IS - 4
M1 - PMID: 38387741
ER -