Having blown a pre-fight drug test with a testosterone-to-epitestosterone ratio of 14:1 (Nevada's legal limit is 6:1), Overeem lost his spot as the number one contender.
Oddsmakers have already released lines for the new title fight, with dos Santos being cast as the sizeable favorite over Mir. Gambling websites Bovada and BetUS both have the champion listed as a -550 (5.5-to-1) favorite over Mir, a +350 (3.5-to-1) underdog.
The 27-year-old Brazilian champion has amassed an 8-0 record inside the octagon, having taken out many of the division's best en route to knocking out Cain Velasquez to win the title this past November.
A veteran of the mixed martial arts world, Mir is currently riding a three-fight winning streak.
UFC 146 is expected to take place on May 26 at the MGM Grand Garden Arena in Las Vegas.
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