The U.S. government says it has reached milestone in the decades-long war on drugs: The Cali cartel, once the biggest drug trafficking organization in the world, is no more.

The Treasury Department on Thursday removed 308 people and entities from its financial sanctions list, the largest ever single such de-listing. Treasury officials say the Cali cartel is now considered defunct.

The move affects 78 people and 230 companies, real estate holdings and other entities the United States claims were used for money laundering during the heyday of the cartel named for the southern Colombian city famed for its music and mountains.

Cartel leaders Miguel and Gilberto Rodriguez Orejuela, who were both first placed on the sanctions list in 1995, are serving 30-year prison sentences after pleading guilty in 2006 in Miami to drug trafficking charges. As part of their plea agreement they surrendered $2.1 billion in assets around the world.

After the brothers’ guilty plea, 28 members of their family signed agreements with the United States to sever ties to narco-trafficking and to surrender assets to the Colombian government.

“Today’s action demonstrates the successful use of targeted sanctions, which have destroyed the Rodriguez Orejuela brothers’ business empire,” said Director of the Office of Foreign Assets Control Adam J. Szubin in a statement.

“The sustained economic pressure on the Cali cartel, at its height the most powerful drug trafficking organization in the world, stemmed from close coordination between multiple U.S. law enforcement agencies and our Colombian counterparts,” Szubin said.

The Cali cartel has been replaced by other drug trafficking groups, even as Colombia has made strides to reduce drug violence and reclaim cities and other parts of the country that were once controlled by cartel gangs and rebel factions that aided trafficking.

In recent years, U.S. authorities say there’s been the rise of so-called Bandas Criminales, criminal gangs who operate trafficking businesses.

A senior Treasury official, in a conference call with reporters Thursday, acknowledged the drug trade remains robust, but said: “It’s a very significant thing to take down a cartel.”

The official said the newer organizations are more manageable for authorities to deal with.

Treasury’s OFAC also says the action illustrates that the sanctions list is always under review. It has removed more than 800 persons from its specially designated nationals and blocked persons sanctions list since 2012 and more than 1,300 in the past seven years.