Work

SAR-Guided Scaffold Innovation of Selective V 2 R Antagonists: Therapeutic Frontiers in ADPKD

Year: 2026

Type: editorial

Abstract: High Resolution Image Download MS PowerPoint Slide The vasopressin V 2 receptor (V 2 R) is a class A G protein–coupled receptor (GPCR) that plays a pivotal role in the regulation of renal water homeostasis and has been implicated in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD) through sustained activation of cyclic adenosine monophosphate (cAMP) signaling. Pharmacological antagonism of V 2 R has emerged as a clinically validated strategy for attenuating cyst growth. However, the therapeutic application of currently available V 2 R antagonists remains constrained by safety liability and a relatively narrow chemical space. A recent study employed systematic structure–activity relationship (SAR) analyses to expand existing design paradigms for V 2 R antagonists, leading to the identification and synthesis of a series of structurally diverse V 2 R antagonist analogues. Supported by multidimensional pharmacological evaluations, these findings provide an important framework for the rational design and optimization of next-generation therapeutics for ADPKD.

Source: ACS Medicinal Chemistry Letters

DOI: 10.1021/acsmedchemlett.6c00105

Authors: Haofeng Shi, Yinlong Li, Steven H. Liang

Institutions: Emory University, Georgia Institute of Technology, The Wallace H. Coulter Department of Biomedical Engineering

Language: English

Topic: Genetic and Kidney Cyst Diseases

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,500