What question did this study set out to answer?

The research aims to explore the efficacy of GV-001 as a selective HDAC6 inhibitor in treating ADPKD.

April 8, 2026Open Access

GV-001, An Oral Available Histone Deacetylase 6 Inhibitor for the Treatment of Autosomal Dominant Polycystic Kidney Disease

SWSian-Siou WuNational Taiwan University PHPei-Yun HungG1 Therapeutics (United States)TYT.Y. YehNational Taiwan University

Key Points

The research aims to explore the efficacy of GV-001 as a selective HDAC6 inhibitor in treating ADPKD.
Designed and synthesized quinazoli-4-one derivatives, including GV-001
Conducted enzyme inhibition and immunoblotting assays to assess potency
Used the BioMAP fibrosis panel and an in vitro human kidney cyst model for functional analysis
Evaluated oral bioavailability and therapeutic efficacy in animal models
GV-001 exhibited a potent enzyme inhibition with an IC50 of 1.18 nM
Effectively reduced inflammatory markers like sIL-6 and Collagen I
Significantly suppressed cyst growth in vitro and in a mouse model
Demonstrated favorable oral bioavailability of 36% in rats

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is a rare genetic disorder characterized by progressive cyst formation. Emerging evidence suggests that histone deacetylase 6 (HDAC6) plays a pivotal role in the regulation of disease progression. In this study, a series of quinazoli-4-one derivatives were designed and synthesized, among which compound 6a (GV-001) exhibited superior potency and selectivity in both enzyme inhibition (IC50 = 1.18 nM) and immunoblotting assays. Subsequent analysis using the BioMAP fibrosis panel and an in vitro human kidney cyst model revealed that GV-001 mitigates inflammatory and fibrotic markers, such as sIL-6 and Collagen I, while effectively suppressing cyst growth. Additionally, GV-001 displayed favorable oral bioavailability (36%) and kidney exposure (AUC(0-t): 1790 ng·h/mL) in rats, whereas oral administration produced significant therapeutic efficacy in an ADPKD mouse model, along with upregulation of PC1 expression. These results support GV-001 as a promising and selective HDAC6 inhibitor for the treatment of ADPKD.

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Cite This Study

Wu et al. (Mon,) studied this question.

synapsesocial.com/papers/69d5f00974eaea4b11a797f9 https://doi.org/https://doi.org/10.1021/acs.jmedchem.5c03139

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