CI-994

CI-994 (N-acetyldinaline) is a novel oral agent which inhibits HDAC1, with a wide spectrum of antitumor activity in preclinical models, in vitro and in vivo. CI-994 inhibits growth of LNCaP cell with IC50 of 7.4 μM. CI-994 inhibits growth of rat leukemia BCLO cells with IC50 of 2.5 μM. The effect of CI-994, as demonstrated by recovery experiments, was cytostatic and seemed to be superimposable in both cell lines. Cytofluorimetric analysis to assess cell cycle perturbation and apoptosis was performed after 24 h of treatment, indicating a cell block with concomitant increase at G0/G1 phase, a reduction at S phase level at 20, 40, 80, and 160 microM, and apoptosis at the higher concentration (160 microM). CI-994 is currently in a phase III clinical trial in patients with lung cancer.