By Racinguk.com staff
The Galileo colt appears the trainer's main contender for this year's £700,000 renewal, having been given a break since he defeated Cracksman at the Curragh at the start of July.
O'Brien could also call upon the lightly-raced Abyssinian, Air Supremacy, Douglas Macarthur, The Anvil and Venice Beach.
The Ballydoyle handler first won the Doncaster Classic with Milan in 2001 and since added to his tally with Brian Boru (2003), Scorpion (2005) and Leading Light (2013).
The son of Sea The Stars was placed in the Dante at York and the King Edward VII Stakes at Royal Ascot before he impressed in last month's Gordon Stakes at Goodwood.
Jim Crowley has been booked to partner Crystal Ocean for the first time.
John Gosden, who has claimed the St Leger four times, is set to saddle Goodwood Cup winner Stradivarius.
Gosden has also left in Coronet, who is the only filly in a potential field of 13 runners. The grey daughter of Dubawi was last seen chasing home esteemed stablemate Enable in the Yorkshire Oaks.
Defoe has won his last four starts for Roger Varian and is poised to step up to Group One level for the first time.
Raheen House is also a major contender for Brian Meehan, having won the Bahrain Trophy at Newmarket in July.
Andrew Balding's Count Octave and the Joseph O'Brien-trained Rekindling were also left in contention at the confirmation stage.