HDAC-IN-54

HDAC-IN-54 is an HDAC inhibitor with an IC50 of 25 nM for human HDAC1, 66 nM for HDAC2, 6.5 nM for HDAC3, and 281 nM for HDAC6. It induces acetylation of α-tubulin and histone H3. HDAC-IN-54 can synergize with cisplatin to induce apoptosis in cancer cells and is applicable in research related to head and neck cancer, ovarian cancer, and tongue squamous cell carcinoma.

HDAC-IN-54 (Compound 4j) effectively inhibits HDAC activity in A2780, A2780CisR, Cal27, and Cal27CisR cells, demonstrating IC50 values of 0.48, 0.32, 0.27, and 0.35 μM respectively, after 18 hours. After 72 hours, it decreases cell viability in these cell lines with IC50 values of 0.47, 1.62, 0.44, and 1.13 μM. In 90 minutes, HDAC-IN-54 powerfully suppresses recombinant human HDAC1-3 and HDAC6 enzymes, showing the strongest inhibitory activity against HDAC3 (IC50 = 6.5 nM), followed by HDAC1 (25.0 nM), HDAC2 (66 nM), and HDAC6 (281 nM), while exhibiting weak activity against HDAC8 (2750 nM). At 10 μM for 24 hours, it induces acetylation of α-tubulin and histone H3 in Cal27 and Cal27CisR cells, confirming its dual inhibition of Class I HDACs and HDAC6. Additionally, HDAC-IN-54 at 250-500 nM with 48 hours of preincubation enhances Cisplatin sensitivity in a concentration-dependent manner in Cal27 and Cal27CisR cells, and synergistically increases Cisplatin-induced apoptosis in these cell lines.