1.
J Med Chem
; 49(2): 441-4, 2006 Jan 26.
Article
in English
| MEDLINE
| ID: mdl-16420026
ABSTRACT
The role of MEK 1,2 in cancer tumorgenesis has been clearly demonstrated preclinically, and two selective inhibitors are currently undergoing clinical evaluation to determine their role in the human disease. We have discovered 4-(4-bromo-2-fluorophenylamino)-1-methylpyridin-2(1H)-ones as a new class of ATP noncompetitive MEK inhibitors. These inhibitors exhibit excellent cellular potency and good pharmacokinetic properties and have demonstrated the ability to inhibit ERK phosphorylation in HT-29 tumors from mouse xenograft studies.
Subject(s)
Aniline Compounds/chemical synthesis , Antineoplastic Agents/chemical synthesis , MAP Kinase Kinase 1/antagonists & inhibitors , MAP Kinase Kinase 2/antagonists & inhibitors , Pyridines/chemical synthesis , Aniline Compounds/pharmacokinetics , Aniline Compounds/pharmacology , Animals , Antineoplastic Agents/pharmacokinetics , Antineoplastic Agents/pharmacology , Cell Line , Cell Line, Tumor , Cell Membrane Permeability , Cell Survival/drug effects , Drug Stability , Hepatocytes/metabolism , Humans , In Vitro Techniques , Mice , Phosphorylation , Pyridines/pharmacokinetics , Pyridines/pharmacology , Rats , Solubility , Structure-Activity Relationship , Xenograft Model Antitumor Assays
2.
J Steroid Biochem Mol Biol
; 89-90(1-5): 5-12, 2004 May.
Article
in English
| MEDLINE
| ID: mdl-15225738
ABSTRACT
The new 24-phenylsulfone 4a, a low-calcemic analog of the natural hormone 1alpha,25-dihydroxyvitamin D(3), is a potent (IC(50) = 28nM) and highly selective inhibitor of the human 24-hydroxylase enzyme CYP24.
Subject(s)
Calcitriol/pharmacology , Cytochrome P-450 Enzyme Inhibitors , Enzyme Inhibitors/pharmacology , Steroid Hydroxylases/antagonists & inhibitors , Sulfones/chemistry , Animals , Calcitriol/analogs & derivatives , Cell Line , Chromatography, High Pressure Liquid , Chromatography, Thin Layer , Enzyme Inhibitors/chemistry , Humans , Spectrum Analysis , Transcription, Genetic/drug effects , Vitamin D3 24-Hydroxylase
3.
Angew Chem Int Ed Engl
; 41(9): 1572-5, 2002 May 03.
Article
in English
| MEDLINE
| ID: mdl-19750669
4.