GV-001 is a potent, selective and orally bioavailable HDAC6 inhibitor with IC50 of 1.18 nM, shows >200- and 1900-fold selectivity over HDAC1 and HDAC8.
GV-001 inhibits tubulin deacetylation in a dose-dependent manner with IC50 of 0.19 uM for Ac-α-tubulin, exhibits selective upregulation of acetylated α-tubulin expression.
GV-001 significantly decreased inflammation-related markers (I-TAC, sIL-6, MCP-1), modulation of fibrosis-related matrix proteins (decreased Collagen I and III; increased Collagen IV; modulated MMP-1), and reduces tissue remodeling/wound healing markers (tPA, uPA, sVEGF).
GV-001 attenuates the expression of inflammatory and immunoregulatory chemokines, EMT markers, and ECM components in human primary cell-based models of renal fibrotic diseases.
GV-001 inhibits the growth of human ADPKD cysts in vitro.
GV-001 (0, 60, or 120 mg/kg) attenuates the progression of cyst growth in the ADPKD mouse model.