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The Queen's Estimate is one of 19 confirmations for the Gold Cup at Royal Ascot on Thursday.
The Sir Michael Stoute-trained filly is already a winner at the Royal meeting having struck in last summer's Queen's Vase, and she booked her place in the two-and-a-half-mile Group One by making a winning return in the Sagaro Stakes at Ascot at the start of May.
Attempting to spoil the party will be 2010 Gold Cup hero Rite Of Passage, who has been restricted to just two competitive starts in the last three years due to injury.
Dermot Weld's stayer looked better than ever, however, when making a winning return in the British Champions Long Distance Cup last October.
Rite Of Passage spearheads a strong Irish challenge, with Weld also leaving in Saval Beg Stakes scorer Pale Mimosa.
Last year's Gold Cup third Saddler's Rock will be looking to bounce back to form following a disappointing spring campaign in Dubai for John Oxx.
Ireland's champion National Hunt trainer Willie Mullins could saddle Simenon, who won twice at last year's Royal meeting in lesser company, while Aidan O'Brien's sole representative is outsider El Salvador.
Other contenders include last year's winner Colour Vision, James Fanshawe's High Jinx, the Ed Dunlop-trained Times Up and possible French raider Top Trip.