Thought Worthy won the Neptune Investment Management Great Voltigeur Stakes at York under a fine ride.
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William Buick settled the three year old out in front in the mile and a half Group Two contest and the pair were never headed.
Buick wound the pace up as the field began to turn for home and, although Main Sequence edged closer under Ted Durcan, stole a three or four length advantage as he kicked into the long straight.
That move proved crucial as the three year old only had a neck in hand over the favourite at the line.
Main Sequence carried his head a little high in the straight and wasn't helped by the eventual winner edging to his right under a left hand drive but he could only gradually eat into the deficit and the line came too soon.
Energizer was never out of last place while Encke and Thomas Chippendale failed to cope with Thought Worthy's injection of pace.
The run of Noble Mission, meanwhile, is best forgotten as Sir Henry Cecil's charge pulled his chance away in the early furlongs of the race in his first start without a hood since his debut.
This was John Gosden's third win in the race in six years following his 2007 success with his Leger hero Lucarno and again in 2008 Centennial.
Buick said: "He galloped well and stayed very well.
"He battled on well and stuck his head out.
"You have to admire a horse like this because he always tries his best."
Gosden said: "The great thing about having an outside draw in a small field is that you can watch everyone.
"William gave him a very smart ride and nicked three lengths travelling into the home straight.
"His brother (Lucarno) won this and went to the Leger and won.
"There is no reason why he shouldn't run either. We always thought he could be a Leger horse."
Gosden is intent on putting up a strong challenge to Triple Crown-seeking Camelot at Doncaster on September 15.
"They are all there to run (in the Leger) if they are in good order," said the Clarehaven handler.
"Shantaram was due to come here but he had mucus in his lungs and Great Heavens has improved all year.
"They (the owners) have been talking about the Prix Vermeille (for Great Heavens), but we'll see."
Lanigan said of Main Sequence: "It turned into a bit of a sprint and it's just one of those things.
"He's done nothing wrong, but we'll see how he is and how he comes out of this before we make any plans.
"Take nothing away from the winner, William Buick rode a great race."
Sky Bet cut the winner to 14-1 from 20s for next month's St Leger at Doncaster.