California Chrome, winner of his last four races, is primed to shine as the 140th Kentucky Derby kicks off US flat racing's Triple Crown.

The chestnut colt trained by Art Sherman was installed as the early 5-2 favourite for the $US2 million ($A2.16 million), 1-1/4-mile race at Churchill Downs, where he will break from the fifth post under jockey Victor Espinoza.

"I think it's a perfect spot," said Sherman. "I think if we break clean, he'll get out of a lot of trouble."

At 77, Sherman could become the oldest trainer to condition a Derby winner on Saturday (Sunday AEST). Hall of Famer Charlie Whittingham, another Californian, won the race at 76.

The week in Kentucky has had Sherman recalling his only prior trip to the Derby 59 years ago - as a stable hand for legendary 1955 winner Swaps.

Despite the pressures that come with saddling a Kentucky Derby favourite, Sherman was enjoying the experience.

"I'm going to go to the parties, relax and have a good time," he said.

The 5-2 odds on California Chrome make him one of the strongest pre-race favourites of recent years. Orb won as 7-2 early favourite last year.

Hoppertunity, the colt trained by Hall of Famer Bob Baffert that was made the early second choice at 6-1, was taken out of the running with a left front hoof issue on Thursday, Baffert saying he'd point the horse at the Preakness, second leg of the Triple Crown, on May 17.

The series concludes with the 1 1/2-mile Belmont Stakes on June 7.

The last horse to achieve the coveted treble was Affirmed in 1978.

California Chrome established himself as the stand-out among this year's crop of three-year-olds with dominant victories in the Grade Two San Felipe and the Grade One Santa Anita Derby, dominating fields that included graded stakes winners by a combined 12 lengths.

With Hoppertunity out, the main threats to California Chrome include Wicked Strong and Danza.