hdac1/6-in-1

HDAC1 6-IN-1 is a potent multi-target inhibitor of GLP (IC50: 1.3 nM), HDAC6 (IC50: 13 nM) and HDAC1 (IC50: 89 nM). HDAC1 6-IN-1 inhibits the methylation and deacetylation of H3K9 at the protein level. HDAC1 6-IN-1 can block the cell cycle of cancer cells in G0 G1 phase, induce apoptosis and prevent cancer cell migration and invasion.

BG45 is an HDAC I type inhibitor with IC50 of 289 nM, 2.0 μM, 2.2 μM and >20 μM for HDAC3 1 2 6 in cell-free assays, respectively.

ROCK HDAC-IN-1 (Compound 10h) serves as an orally effective inhibitor of ROCK HDAC. This compound suppresses ROCK1 2 (IC50: 254.9 nM, 58.18 nM) and HDAC1 2 3 6 8 (IC50: 9.09, 8.03, 6.26, 0.41, 7.69 nM). It stimulates the activation of DAMPs, notably calreticulin (CRT) exposure and HMGB1 release, suggesting its potential as an inducer of immunogenic cell death (ICD). ROCK HDAC-IN-1 exhibits antiproliferative effects against breast cancer cells (IC50: 0.37 μM for MDA-MB-231 cells), inhibits tumor growth, activates T cells, and shows no significant toxicity.

CDK4 6 HDAC-IN-1 (Compound N14) is a dual-target inhibitor of CDK4 6 and HDAC, with IC50 values of 7.23 nM for CDK4, 13.20 nM for CDK6, 55.66 nM for HDAC1, and 48.38 nM for HDAC6. It induces apoptosis and G0 G1 phase arrest through the HDAC-p21-CDK signaling pathway and can inhibit hepatocellular carcinoma.

Givinostat (ITF-2357) is an HDAC inhibitor with IC50 values of 198 nM for HDAC1 and 157 nM for HDAC3.

HDAC8 BRPF1-IN-1 (Compound 23a) is a dual inhibitor targeting human HDAC8 (IC50: 443 nM) and human BRPF1 (Kd: 67 nM), with low in vitro activity against HDAC1 and HDAC6.

HDAC-IN-53 is an orally active, selective inhibitor of HDAC1-3, with IC50 values of 47 nM, 125 nM, and 450 nM, respectively. It exhibits no inhibitory effects on class II HDACs (HDAC4, 5, 6, 7, 9; IC50 >10 μM). The compound induces caspase-dependent apoptosis and significantly hampers the growth of human tumor xenografts in nude mice and murine tumor growth in immune-competent mice with MC38 colon cancer [1].

HDAC6-IN-33 (compound 6), an irreversible and selective HDAC6 inhibitor, demonstrates a potency with an IC 50 of 193 nM and lacks activity against HDAC1-4. This compound adheres to HDAC6 through a two-step slow-binding mechanism, establishing it as a tight-binding inhibitor [1].