PTGER4 and arthritic joint disease: While no human data are available on whether EP4 antagonists can cause cardiovascular toxicity, an EP4 antagonist AAT-007 used in phase 1/2 trials in >800 human arthritis patients was well tolerated in pharmacologically effective doses (300 mg orally twice daily), with no evidence of dose-limiting toxicity (Dr. Yukinori Take, Ask/At, Japan, personal communication, cited with permission).