Abstract
The design, synthesis, and biological evaluation of N-(2-aminophenyl)-4-[(4-pyridin-3-ylpyrimidin-2-ylamino)methyl]benzamide 8 (MGCD0103) is described. Compound 8 is an isotype-selective small molecule histone deacetylase (HDAC) inhibitor that selectively inhibits HDACs 1-3 and 11 at submicromolar concentrations in vitro. 8 blocks cancer cell proliferation and induces histone acetylation, p21 (cip/waf1) protein expression, cell-cycle arrest, and apoptosis. 8 is orally bioavailable, has significant antitumor activity in vivo, has entered clinical trials, and shows promise as an anticancer drug.
MeSH terms
-
Administration, Oral
-
Animals
-
Benzamides / administration & dosage
-
Benzamides / chemistry
-
Benzamides / pharmacology*
-
Dogs
-
Drug Screening Assays, Antitumor
-
Enzyme Inhibitors / administration & dosage
-
Enzyme Inhibitors / chemistry
-
Enzyme Inhibitors / pharmacology*
-
Enzyme-Linked Immunosorbent Assay
-
Female
-
Flow Cytometry
-
Histone Deacetylase Inhibitors*
-
Humans
-
Male
-
Pyrimidines / administration & dosage
-
Pyrimidines / chemistry
-
Pyrimidines / pharmacology*
-
Rats
-
Rats, Sprague-Dawley
-
Structure-Activity Relationship
Substances
-
Benzamides
-
Enzyme Inhibitors
-
Histone Deacetylase Inhibitors
-
Pyrimidines
-
mocetinostat