Flames ripped through the roof of the boarded-up building located near the intersection of Los Angeles and 3rd streets. The blaze erupted just after 7:30 p.m., according to the Los Angeles Fire Department.
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Smoke billowed from the building after most of the flames were extinguished an hour later.
It is unclear what sparked the blaze. No injuries were immediately reported.
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About 135 firefighters battled the fire.
The building was red-tagged. LAFD says an official knockdown won't be declared most likely until Thursday morning.