Therapeutic Efficacy of a Novel Pharmacologic GRK2 Inhibitor in Multiple Animal Models of Heart Failure

IF 8.4 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

JACC: Basic to Translational Science Pub Date : 2025-02-01 DOI:10.1016/j.jacbts.2024.10.008

Rajika Roy PhD , Sarah M. Schumacher PhD , Haley Christine Murphy BS , Jessica Grondolsky , Thiele Osvaldt Rosales PhD , J. Kurt Chuprun PhD , Erhe Gao MD, PhD , Huaqing Zhao PhD, MS , Remus M. Berretta BS , Alexander R.H. Hobby PhD , Steven R. Houser PhD , Larisa V. Avramova PhD , John J.G. Tesmer PhD , Walter J. Koch PhD

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引用次数: 0

Abstract

GRK2 is the most prominent G protein-coupled receptor kinase that is upregulated in heart failure (HF), and inhibiting GRK2 has improved cardiac function in mice. CCG258208, generated from the paroxetine scaffold, which has GRK2 inhibitory properties, has a 50-fold higher selectivity for GRK2 at 100-fold lower doses. We evaluated CCG258208 in 2 mice HF models and found that CCG258208 has robust therapeutic effects. In a chronic mini-swine HF model, acute administration of CCG258208 enhanced dobutamine inotropic responses. Our results indicate that CCG258208 has robust cardioprotective and HF-reversing effects in different HF models and it stands as a promising lead for HF therapy.

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来源期刊

JACC: Basic to Translational Science CARDIAC & CARDIOVASCULAR SYSTEMS-

CiteScore

14.20

自引率

1.00%

发文量

161

审稿时长

16 weeks

期刊介绍： JACC: Basic to Translational Science is an open access journal that is part of the renowned Journal of the American College of Cardiology (JACC). It focuses on advancing the field of Translational Cardiovascular Medicine and aims to accelerate the translation of new scientific discoveries into therapies that improve outcomes for patients with or at risk for Cardiovascular Disease. The journal covers thematic areas such as pre-clinical research, clinical trials, personalized medicine, novel drugs, devices, and biologics, proteomics, genomics, and metabolomics, as well as early phase clinical trial methodology.