Second Generation ARA Compounds
Our three next generation ARA compounds are structural analogues of acadesine, each of which exhibits more potent adenosine-mediated, cardioprotective activity than acadesine. The safety of these compounds has been evaluated in Phase I clinical trials. These compounds show promise of providing cardioprotective clinical benefit to patients in surgical settings beyond CABG surgery and in acute cardiovascular settings.
We have an open IND for GP531 that has been studied in numerous preclinical models of ischemia-reperfusion injury and its safety has been demonstrated in Phase I clinical studies in normal volunteers and in a pilot Phase II study in patients with coronary artery disease. GP531 appears to possess important advantages relative to the first generation ARA compound that include
- GP531 does not metabolize to uric acid as does acadesine. This permits longer durations of therapy.
- GP531 has been shown to have greater potency in preclinical models of ischemia-reperfusion injury.
- GP531 has a longer plasma half-life.
- GP531 has greater oral bioavailablity
We have initiated preclinical evaluation of this novel compound in acute settings beyond ischemia-reperfusion injury, and if successful, we will initiate Phase II clinical studies in 2009.