Discovery of β-Arrestin Biased, Orally Bioavailable, and CNS Penetrant Neurotensin Receptor 1 (NTR1) Allosteric Modulators
نویسندگان
چکیده
منابع مشابه
Discovery of positive allosteric modulators and silent allosteric modulators of the μ-opioid receptor.
μ-Opioid receptors are among the most studied G protein-coupled receptors because of the therapeutic value of agonists, such as morphine, that are used to treat chronic pain. However, these drugs have significant side effects, such as respiratory suppression, constipation, allodynia, tolerance, and dependence, as well as abuse potential. Efforts to fine tune pain control while alleviating the s...
متن کاملThe effects of deleting the mouse neurotensin receptor NTR1 on central and peripheral responses to neurotensin.
Mice deficient in the neurotensin (NT)-1 receptor (NTR1) were developed to characterize the NT receptor subtypes that mediate various in vivo responses to NT. F2 generation (C57BL6/Sv129J) NTR1 knockout (-/-) mice were viable, and showed normal growth and overt behavior. The -/- mice lacked detectable NTR1 radioligand binding in brain, whereas NTR2 receptor binding density appeared normal compa...
متن کاملβ-Arrestin and dishevelled coordinate biased signaling.
T he adaptor proteins β-arrestins 1 and 2 are ubiquitously expressed and were originally discovered for desensitizing G proteinmediated signal transduction by the cellsurface seven-transmembrane receptors (7TMRs or GPCRs) (1). 7TMRs constitute the largest family of cell-surface receptors, and their signaling regulates almost every aspect of mammalian physiology, including vision, olfaction, beh...
متن کاملMechanisms of Biased β-Arrestin-Mediated Signaling Downstream from the Cannabinoid 1 Receptor
Activation of G protein-coupled receptors results in multiple waves of signaling that are mediated by heterotrimeric G proteins and the scaffolding proteins β-arrestin 1/2. Ligands can elicit full or subsets of cellular responses, a concept defined as ligand bias or functional selectivity. However, our current understanding of β-arrestin-mediated signaling is still very limited. Here we provide...
متن کاملβ-Arrestin-biased signaling mediates memory reconsolidation.
A long-standing hypothesis posits that a G protein-coupled signaling pathway mediates β-adrenergic nervous system functions, including learning and memory. Here we report that memory retrieval (reactivation) induces the activation of β1-adrenergic β-arrestin signaling in the brain, which stimulates ERK signaling and protein synthesis, leading to postreactivation memory restabilization. β-Arrest...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Journal of Medicinal Chemistry
سال: 2019
ISSN: 0022-2623,1520-4804
DOI: 10.1021/acs.jmedchem.9b00340