LSQ-28 is a potent, selective HDAC3 inhibitor with IC50 of 42 nM, >150-fold selective over HDAC1, HDAC2, and HDAC6.
LSQ-28 does not inhibit HDAC4, 5, 7–10 at concentrations up to 10 μM, but inhibits HDAC11 with an IC50 value of 8.87 μM.
LSQ-28 exhibits antiproliferative activities across HCT-116 (colorectal carcinoma), 4T1 (breast cancer), B16-F10 (melanoma), and SK-OV-3 (ovarian cancer) with IC50 of 5.558 to 12.49 μM.
LSQ-28 inhibits B16-F10 cell migration, markedly reduces the invasive capacity, possesses apoptotic potential.
LSQ-28 (5, 10, and 20 μM) induced a significant increase in Ac-H3 levels in B16-F10 and 4T1 cells.
LSQ-28 induces a dose-dependent degradation in PD-L1 levels in B16-F10 cells.
LSQ-28 enhancse the antitumor activity of PARP inhibitors through a synergistic enhancement of the DNA-damage response.
Combination treatment of LSQ-28 and olaparib significantly enhanced TGI, achieving a TGI of 91% in in 4T1 tumor xenograft models.