CI-994 (N-acetyl-dinaline) in combination with conventional anti-cancer agents is effective against acute myeloid leukemia in vitro and in vivo

Oncol Rep. 2008 Jun;19(6):1517-23. doi: 10.3892/or.19.6.1517.


N-acetyl-dinaline (CI-994) is an investigational anti-cancer drug which inhibits histone deacetylases. We evaluated the interaction between CI-994 and conventional chemotherapeutics used in acute myeloid leukemia (AML) in a rat model for AML and Brown Norway rat acute myelocytic leukemia (BNML). In vitro, CI-994 in combination with cytarabine (ara-C), daunorubicin and mitoxantrone, resulted in moderate synergism. In vivo, higher dosages of CI-994 induced complete remissions. CI-994/ara-C was very active against BNML. The combinations of CI-994/daunorubicin and CI-994/mitoxantrone were also active against BNML. This study demonstrates favorable in vitro and in vivo interactions between CI-994 and conventional anti-cancer agents used for the treatment of AML.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Benzamides
  • Blood Cell Count
  • Cell Proliferation / drug effects*
  • Cytarabine / administration & dosage
  • Daunorubicin / administration & dosage
  • In Vitro Techniques
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / metabolism
  • Leukemia, Myeloid, Acute / pathology
  • Male
  • Mitoxantrone / administration & dosage
  • Phenylenediamines / administration & dosage*
  • Rats
  • Rats, Inbred BN


  • Benzamides
  • Phenylenediamines
  • Cytarabine
  • Mitoxantrone
  • tacedinaline
  • Daunorubicin