Federal authorities said they dealt a major blow to Mexico’s bloodiest drug cartel, wrapping up a six-month probe Wednesday with 100 search warrants and 250 busts nationwide.

Dubbed “Project Python,” the joint DEA and US Justice Department operation turned up the heat on the Cartel de Jalisco Nueva Generación and its notorious leader, Nemesio “El Mencho” Oseguera-Cervantes, one of the most sought-after drug kingpins in the world.

“These arrests punctuate the many other arrests of mid- and high-level CJNG members since Project Python began,” Acting DEA Administrator Uttam Dhillon said at a press conference Wednesday.

“During the course of this six-month operation, DEA has arrested over 700 subjects associated with CJN, seized more than 20,000 kilograms of drugs — including over 15,000 kilograms of methamphetamine — and over $22 million worth of money and assets,” Dhillon said.

Assistant US Attorney Brian Benczkowski called the cartel “one of the most dangerous transnational criminal organizations in the world.”

“The cartel has its hands in trafficking multiple deadly substances,” Benczkowski said. “It’s responsible for moving tons of cocaine, methamphetamine and fentanyl-laced heroin into the United States and elsewhere around the globe.”

Federal officials also announced a new superseding indictment against El Mencho — one month after his son, Ruben “El Menchito” Oseguera-Gonzalez, was extradited to the US and is awaiting trial.

Officials called the cartel “the most well-armed cartel” in Mexico, with a wide-reaching distribution network that includes hubs in New York, Los Angeles, Chicago, Houston and Atlanta.

DEA Special Agent In Charge Ray Donovan called it “a domineering threat to people’s safety on both sides of the Southwest border.”

“These seizures leave no doubt that CJNG has targeted New York as a transshipment and destination point for their business plan,” Donovan said.

The Jalisco cartel made headlines in January when one of the drug gang’s curvacious assassin, 21-year-old Maria Guadalupe Lopez Esquivel, known as “La Catrina,” was killed in a shootout with authorities.