AG-3340 (Agouron Pharmaceuticals Inc).

Area of Science:

• Oncology
• Pharmacology

Background:

• Agouron Pharmaceuticals is developing AG-3340 (prinomastat), an oral, non-peptide inhibitor targeting metalloproteinases like MMP-2, MMP-9, MMP-14, and collagenase III.
• The compound has demonstrated significant antimetastatic and antitumor activity in preclinical animal models, alongside favorable oral bioavailability and pharmacokinetics.

Purpose of the Study:

• To evaluate the efficacy and safety of AG-3340 as a potential treatment for various cancers, including lung and prostate cancer.
• To assess AG-3340 in combination with chemotherapy in phase III clinical trials.

Main Methods:

• Phase III clinical trials were initiated for lung and prostate cancers, testing AG-3340 in combination with chemotherapy.
• Pharmacokinetic studies were conducted in healthy volunteers, and dose-escalation studies in patients assessed toxicity.
• Phase I studies evaluated AG-3340 in combination with paclitaxel and carboplatin.

Main Results:

• AG-3340 demonstrated significant antitumor and antimetastatic activity in animal models, with oral doses halting tumor growth and reducing metastasis.
• Phase I studies indicated that AG-3340 was safe and well-tolerated, with joint-related toxicities not being dose-limiting.
• Encouraging results from phase I and preclinical studies were presented, and a combination study with paclitaxel and carboplatin was found to be safe.

Conclusions:

• AG-3340 exhibits promising antimetastatic and antitumor properties, supported by preclinical data and early clinical safety findings.
• Ongoing phase III trials are crucial for confirming the efficacy of AG-3340 in combination chemotherapy regimens for lung and prostate cancers.
• While Roche discontinued collaboration, Agouron continues to investigate AG-3340 analogs, indicating ongoing interest in this class of compounds.