I have been trying to find recent info about AG3340 but just about all I have found is the following reference. Great news for rats, especially if they are heavy smokers. I hope the results are relevant also for humans. Maybe somebody more qualified than I could comment on the results.
Title
Rodent pharmacokinetic and anti-tumor efficacy studies with a series of synthetic inhibitors of matrix metalloproteinases.
Author
Santos O; McDermott CD; Daniels RG; Appelt K
Address
Agouron Pharmaceuticals, Inc., San Diego, CA, USA. ice9@pacbell.net
Source
Clin Exp Metastasis, 15(5):499-508 1997 Sep
Abstract
Matrix metalloproteinases are a family of zinc-containing proteases that degrade extracellular matrix and basement
membranes. These enzymes are thought to play a role in processes essential for tumor growth, invasion, and metastasis.
Here we report pharmacokinetic and anti-tumor efficacy studies with a series of structurally related inhibitors of these
enzymes that were synthesized at Agouron Pharmaceuticals using protein structure based drug design. The compounds
studied were AG3287, AG3293, AG3294, AG3296, AG3319, and AG3340. Rat oral bioavailability ranged from 15
to 68%. Despite similar profiles of enzyme inhibition across the family of enzymes, and similar pharmacokinetics
following i.p. administration to mice, efficacy against the Lewis lung carcinoma murine model varied from tumor growth
enhancement, to significant reductions in the size of primary tumors and the number of lung metastases. AG3340 was the
most efficacious compound against the Lewis lung carcinoma model, resulting in the complete cessation of primary tumor
growth throughout the experiment in 4/6 mice treated with daily i.p. injections at a dose of 50 mg/kg. This treatment
inhibited the formation of lung metastases greater than 5 mm in diameter by 90%. |
