CI-994

A potent, selective class I HDAC inhibitor with IC50 of 0.9/0.9/1.2 uM for HDAC1/2/3, respectively; show no significant inhibitory activity against HDAC8 (IC50>20 uM) ; reduces S phase level and increases apoptosis in A-549 and LX-1 cells; demonstrates antitumor activity against several tumor models, including the chemo-resistant mouse pancreatic ductal carcinoma as well as the human prostate tumor model LNCaP.Breast Cancer Phase 2 Discontinued (In Vitro) :Tacedinaline (N-acetyldinaline) is a novel oral compound with a wide spectrum of antitumor activity in preclinical models. The mechanism of action may involve inhibition of histone deacetylation and cell cycle arrest. Tacedinaline (N-acetyldinaline) is combined with antineoplastic agents commonly used in non-small cell lung cancer cell line management, a marked synergism of action (R=1.8, R=1.5) is observed between Tacedinaline (N-acetyldinaline) (40 μM) and gemcitabine (0.01 μM) at 48 and 72 h of treatment. Tacedinaline (N-acetyldinaline) inhibits mitogen-stimulated blood lymphocyte proliferation with an IC50 value of 3 μM. (In Vivo) :Tacedinaline (CI-994) has activity against 8/8 solid tumors tested: pancreatic ductal adenocarcinoma #02 (4.7) ; pancreatic adenocarcinoma #03 (3.0; 1/6 cures) ; colon adenocarcinoma #38 (1.6) ; colon adenocarcinoma #51/A (1.1) ; mammary adenocarcinoma #25 (1.7) ; mammary adenocarcinoma #17/ADR (0.5) ; Dunning osteogenic sarcoma (4.0) ; and the human prostate carcinoma LNCaP (1.2) . CI-994 is the acetylated metabolite of dinaline and has the same spectrum of activity in vivo as dinaline. It also behaves similarly in schedule comparison/toxicity trials. Tacedinaline (CI-994) can effect lymphoid tissue in rats within 1 day of a single oral dose, that effects are generally reversible within 7 days.