Tacedinaline (CI994) is a selective class I HDAC inhibitor with potential antineoplastic activity.

HDAC2:0.9 μM, HDAC3:1.2 μM, HDAC1:0.9 μM

In models of chemotherapy-resistant pancreatic ductal adenocarcinoma in mice and human prostate tumor, CI-994 consistently demonstrated antitumor activity.

CI-994 exhibits antitumor activity, displaying enhanced cytocidal effects in solid tumors. It inhibits cell growth across various cell types, including rat leukemia BCLO cells (IC50=2.5 µM) and LNCaP cells (IC50=7.4 µM). In A-549 and LX-1 cells, CI-994 (<160 mM) increases the number of cells in the G0/G1 phase while decreasing those in the S phase, effectively inhibiting cell growth and inducing apoptosis.

LNCaP cell lines are maintained in RPMI 1640 medium containing 10% fetal bovine serum, 1% penicillin and streptomycin, as the complete culture medium. Cells (2×104) are seeded in 24-well plates and incubated in a 5% CO2 incubator at 37 °C for 1 day. Cultures are treated with CI-994, alone and in combination on day 2 and 4. Cells are washed on day 2 and 4 and media are changed. Mitochondrial metabolism is measured as a marker for cell growth by adding 100 μL/well MTT (5 mg/mL in medium) with 2 hours incubation at 37 °C on Day 6. Crystals formed are dissolved in 500 μL of DMSO. The absorbance is determined using a microplate reader at 560 nm. The absorbance data are converted into cell proliferation percentage. Each assay is performed in triplicate. (Only for Reference)