Molecular Glues: A New Approach to Modulating GPCR Signaling Bias

Biochemistry, Год журнала: 2025, Номер unknown

Опубликована: Фев. 3, 2025

G-protein-coupled receptors (GPCRs) transmit an extracellular chemical/biological signal across the cell membrane, stimulating array of intracellular signaling cascades. Canonically, these molecules bind to endogenous ligand pocket (orthosteric pocket), which stabilizes either active or inactive conformational ensemble receptor. However, recent structural evidence indicates that small can mediate protein–protein interactions between GPCR and their transducers. These are reminiscent molecular glues be powerful tools for modulating bias. In this Perspective, we will investigate current information available on how they modulate We also examine prospects drug/probe design.

Язык: Английский

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Principles and Design of Molecular Tools for Sensing and Perturbing Cell Surface Receptor Activity

Chemical Reviews, Год журнала: 2025, Номер unknown

Опубликована: Фев. 25, 2025

Cell-surface receptors are vital for controlling numerous cellular processes with their dysregulation being linked to disease states. Therefore, it is necessary develop tools study and the signaling pathways they control. This Review broadly describes molecular approaches that enable 1) visualization of determine localization distribution; 2) sensing receptor activation permanent readouts as well in real time; 3) perturbing activity mimicking receptor-controlled learn more about these processes. Together, have provided valuable insight into fundamental biology helped characterize therapeutics target receptors.

Язык: Английский

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Cryo-EM as a tool for illuminating activation mechanisms of human class A orphan GPCRs

Pharmacological Reviews, Год журнала: 2025, Номер unknown, С. 100056 - 100056

Опубликована: Апрель 1, 2025

Язык: Английский

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Allostery Illuminated: Harnessing AI and Machine Learning for Drug Discovery

ACS Medicinal Chemistry Letters, Год журнала: 2024, Номер 15(9), С. 1449 - 1455

Опубликована: Авг. 30, 2024

In the past several years there has been rapid adoption of artificial intelligence (AI) and machine learning (ML) tools for drug discovery. this Microperspective, we comment on recent AI/ML applications to discovery allosteric modulators, focusing breakthroughs with AlphaFold, structure-based (SBDD), medicinal chemistry applications. We discuss how these technologies are facilitating remaining challenges identify binding sites ligands.

Язык: Английский

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An introduction to the special issue “Sam Enna legacy of Excellence”

Biochemical Pharmacology, Год журнала: 2024, Номер 228, С. 116510 - 116510

Опубликована: Авг. 30, 2024

Язык: Английский

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