| Attributs | Valeurs |
|---|
| type
| |
| Is Part Of
| |
| Subject
| |
| Title
| - Carbamoylphosphonate Matrix Metalloproteinase Inhibitors 6: cis-2-Aminocyclohexylcarbamoylphosphonic Acid, A Novel Orally Active Antimetastatic Matrix Metalloproteinase-2 Selective InhibitorSynthesis and Pharmacodynamic and Pharmacokinetic Analysis
|
| has manifestation of work
| |
| related by
| |
| Author
| |
| Abstract
| - cis-2-Aminocyclohexylcarbamoylphosphonic acid (cis-ACCP) was evaluated in vitro and in two in vivo cancer metastasis models. It reduced metastasis formation in mice by ∼90% when administered by a repetitive once daily dosing regimen of 50 mg/kg via oral or intraperitoneal routes and was nontoxic up to 500 mg/kg, following intraperitoneal administration daily for two weeks. Pharmacokinetic investigation of cis-ACCP in rats revealed distribution restricted into the extracellular fluid, which is the site of action for the antimetastatic activity and rapid elimination (t1/2 ∼ 19 min) from blood. Sustained and prolonged absorption (t1/2 ∼126 min) occurred via paracellular mechanism along the small and large intestine with overall bioavailability of 0.3%. The in vivo concentrations of cis-ACCP in the blood in rats was above the minimal concentration for antimetastatic/MMP-inhibitory activity, thus explaining the prolonged action following once daily administration. Finally, 84% of the intravenously administered cis-ACCP to rats was excreted intact in the urine.
|
| Alternative Title
| - Metalloproteinase-2 Selective Inhibitor
|
| is part of this journal
| |
