The shooting occurred around 3:50 a.m. in the area of 8th and Bixel streets, near the 110 Freeway, according to LAPD.
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LAPD says officers tried to contact the man, but he ran and pulled out a handgun. Police then opened fire.
The man was transported to a hospital, where he died, LAPD Officer Rosario Cervantes said.
A handgun was recovered at the scene, and the investigation is ongoing, Cervantes said.
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It was unclear why officers initially attempted to contact the man.
The identity of the man was not immediately released. No officer was injured during the incident.