St Leger winner Encke has been euthanised after suffering a hind leg injury during routine exercise.
The five-year-old denied Camelot the historic Triple Crown when he claimed the season's final Classic at Doncaster in 2012 but missed the 2013 season after he was caught caught up in the Mahmood Al Zarooni drugs scandal.
He had returned this summer for trainer Charlie Appleby, running well in defeat in the Glorious Stakes at Goodwood, finishing third in the Irish St Leger and third in the Cumberland Lodge Stakes at Ascot earlier this month.
Appleby said on the Godolphin website Encke had sustained a hind leg injury and following complications, could not be saved.
"His Highness Sheikh Mohammed is deeply saddened at the loss of his Classic winner," Appleby said.
"Encke was a talented racehorse and will be sorely missed as he was one of the yard's favourites."