Tacedinaline (CI994)

HDAC1

269, 3

human prostate tumor model LNCaP

CI-994 is in Phase III clinical trial in patients with Lung Cancer

535 mg/kg

0.57 uM [1], 0.57 uM [1], 0.57 uM [1], 0.57 uM [1], 0.57 uM [1], 0.57 uM [1]

CI-994 exerts demonstrated antitumor activity against several tumor models, including the chemo-resistant mouse pancreatic ductal carcinoma as well as the human prostate tumor model LNCaP. [4]

LNCaP cell lines are maintained in RPMI 1640 medium containing 10% fetal bovine serum, 1% penicillin and streptomycin, as the complete culture medium. Cells (2x104) 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 uL/well MTT (5 mg/mL in medium) with 2 hours incubation at 37 C on Day 6. Crystals formed are dissolved in 500 uL 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.

Tacedinaline (CI994, PD-123654, GOE-5549, Acetyldinaline) is a selective class I HDAC inhibitor with IC50 of 0.9, 0.9, 1.2, and >20 μM for human HDAC 1, 2, 3, and 8, respectively. Phase 3.