Can Targeting the Sodium Site via Water Molecules Lead to the Development of Safer Opioids? DOI Creative Commons
Daniel Wacker, Marta Filizola

ACS Central Science, Год журнала: 2024, Номер 10(8), С. 1436 - 1438

Опубликована: Авг. 8, 2024

Язык: Английский

A cryptic pocket in CB1 drives peripheral and functional selectivity DOI
Vipin Ashok Rangari, Evan S. O’Brien,

Alexander S. Powers

и другие.

Nature, Год журнала: 2025, Номер unknown

Опубликована: Март 5, 2025

Язык: Английский

Процитировано

3
Advances in the structural understanding of opioid allostery DOI Creative Commons
Nokomis Ramos‐Gonzalez, Balázs Varga, Susruta Majumdar

и другие.

Trends in Pharmacological Sciences, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Activation of the μ opioid receptor (MOR) can give analgesia, but also has dangerous side effects. Drugs that target MOR through an allosteric site, meaning they bind outside usual pocket, present a novel mode activation with different pharmacology relative to orthosteric drugs. Recent structural studies valuable new information on how modulators interact MOR.

Язык: Английский

Процитировано

0
Structure-guided design of partial agonists at an opioid receptor DOI Creative Commons
Balázs Varga, Sarah M. Bernhard,

Amal El Daibani

и другие.

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Март 13, 2025

Chronic pain and opioid overdose deaths highlight the need for non-addictive analgesics with novel mechanisms. The δ receptor (δOR) is a promising target, as it lacks respiratory depression associated µ (µOR) agonists. However, early δOR full agonists caused seizures, limiting their clinical use. Partial may offer more controlled activation than agonists, but development has been hindered by uncertainty regarding molecular mechanism of partial agonism. Here we show that C6-Quino, bitopic ligand developed through structure-based design, acts selective agonist. Functional studies reveal C6-Quino shows differential activity at G-protein arrestin pathways interacts sodium binding pocket, confirmed cryo-EM analysis. demonstrates oral activity, analgesic in chronic models without causing δOR-related seizures µOR-related adverse effects which have limited usage recent times. This discovery outlines new strategy developing δOR-targeted provides framework optimizing signaling profiles other Class A GPCRs. δ-Opioid receptors are targets management reduced side effects. Here, authors use approach to design characterize agonist, highlighting its potential therapeutic relevance.

Язык: Английский

Процитировано

0
Rational Design Biased Compounds against μ-Opioid Receptor DOI

Chenyang Wu,

Yi Li, Horst Vogel

и другие.

ACS Pharmacology & Translational Science, Год журнала: 2025, Номер unknown

Опубликована: Апрель 8, 2025

Язык: Английский

Процитировано

0
Can Targeting the Sodium Site via Water Molecules Lead to the Development of Safer Opioids? DOI Creative Commons
Daniel Wacker, Marta Filizola

ACS Central Science, Год журнала: 2024, Номер 10(8), С. 1436 - 1438

Опубликована: Авг. 8, 2024

Язык: Английский

Процитировано

1