STR-V-53 is a novel glycosylated, liver cancer-selective histone deacetylase (HDAC) inhibitor with IC50 of 24.3/60.1/213.43 nM for HDAC1/2/3/6, demonstrates exquisite selective cytotoxicity against human HCC cells.
STR-V-53 exhibits anti-proliferation effect against Hep-G2 and Huh7 cells with IC50 of 10.4 and 6.25 uM respectively, but lack of growth inhibition effect against other cancer cells in the NCI-60 panel.
STR-V-53 shows weak inhibition of HDAC 8 and no inhibition of HDAC 11 at the maximum tested concentration of 10 uM.
STR-V-53 is uptaked by GLUT-2 and blockage of GLUT-2 attenuates the cytotoxicity of STR-V-53 against Hep-G2 HCC cells.
STR-V-53 upregulates PD-L1 and downregulates PD-1 expression, upregulates CD54 (ICAM-1) in HCC cells.
STR-V-53 selectively induces apoptosis in HCC cells, causes cell cycle arrest at the S stage.
STR-V-53 (25, 50 mg/kg, i.p.) effectively suppresses HCC growth in xenograft and murine models of HCC.
STR-V-53 reprogrammed the T cell responses and prolonged median overall survival in an orthotopic HCC model in immunocompetent mice, when combined with anti-PD1 therapy.