There was no immediate word on whether the fire was directly related to the looting.
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The fire broke out around 8 p.m. near 17th and Walnut streets.
Video from Chopper 6 showed flames and smoke erupting from the building.
Chopper 6 over scene of massive fire at 17th and Walnut in Center City
The looting began after an afternoon of peaceful protests in Center City - over the death of George Floyd while he was in custody of Minneapolis police - turned increasingly violent.
Cars were overturned and several vehicles, including police cars, were set on fire.
George Floyd protests turn violent in Philadelphia
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Chopper 6 was overhead as several people skirmished with officers.
In all, more than a dozen officers were injured.
Meanwhile, more than a dozen people have been arrested.