tcsc1280 Tacedinaline

CI-994 (Tacedinaline) is an inhibitor of the histone deacetylase (HDAC) with IC₅₀s of 0.9, 0.9, 1.2 μM for recombinant HDAC 1, 2 and 3 respectively.

IC50 & Target: IC50: 0.9 μM (HDAC 1), 0.9 μM (HDAC 2), 1.2 μM (HDAC 3)^[1]

In Vitro: CI-994 (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. CI-994 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 CI-994 (40 μM) and gemcitabine (0.01 μM) at 48 and 72 h of treatment^[2].CI-994 inhibits mitogen-stimulated blood lymphocyte proliferation with an IC₅₀ value of 3 μM^[4].

In Vivo: 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^[3]. CI-994 can effect lymphoid tissue in rats within 1 day of a single oral dose, that effects are generally reversible within 7 days^[4].