Promising antitumor activity with MGCD0103, a novel isotype-selective histone deacetylase inhibitor.
BACKGROUND
Histone deacetylases (HDACs), which target histones as well as non-histone proteins as substrates, have the potential to regulate aberrant gene expression and restore normal growth control in malignancies.


OBJECTIVE
This review provides an updated summary of preclinical and clinical experience with the oral isotype-selective HDAC inhibitor MGCD0103 in cancer.


METHODS
Data presented in abstract form from international conferences or journal articles found within a PubMed search of article up to May 2008 are described in this review.


CONCLUSIONS
MGCD0103 appears tolerable and exhibits favorable pharmacokinetic and pharmacodynamic profiles with evidence of target inhibition in surrogate tissues. Clinical and pharmacodynamic data support a three-times-weekly administration at a 90-mg fixed dose. MGCD0103 displays promising antitumor activity in hematological and lymphoproliferative diseases.
Le Tourneau
Christophe
C
University of Toronto, University Health Network, Princess Margaret Hospital, Division of Medical Oncology and Hematology, 610 University Avenue, Suite 5-718, Toronto M5G 2M9, Canada.
Siu
Lillian L
LL
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001549:Benzamides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002986:Clinical Trials as Topic; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D007527:Isoenzymes; D009369:Neoplasms / Q000188:drug therapy*; D011743:Pyrimidines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D013379:Substrate Specificity
D000970:Antineoplastic Agents; D001549:Benzamides; D056572:Histone Deacetylase Inhibitors; D007527:Isoenzymes; D011743:Pyrimidines; C523184:mocetinostat