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The group, which expects to raise more than $3 million for the federal candidates it supports, is taking aim at Republicans who opposed the Iran nuclear deal, primarily Republican Senators Mark Kirk of Illinois and Ron Johnson of Wisconsin.
"Our core drive this cycle is to really, fundamentally change the calculus on the politics of diplomacy," J Street national political director Ben Shnider was quoted as saying.
"We want to prove this cycle... that a diplomacy-first approach to foreign policy is not just good policy, but also savvy politics."
J Street intends to support more than 110 candidates this year and has already raised one million dollars for the campaign.
In the 2014 elections, J Street raised $2.4 million and supported 95 candidates. While it is not currently running TV or radio ads, Shnider said that "all tactics are on the table."
The Iran nuclear deal was a bellwether for J Street, which ran a multimillion-dollar TV and print campaign on both the local and the national level in support of President Barack Obama and the deal.
It also surveyed American-Jewish opinion on the deal a number of times and put Israeli and American diplomatic experts in touch with key stakeholders in states where lawmakers were undecided about the deal.
Republican presidential candidates are "seizing on voters' anxiety to set up military intervention in the Middle East," Shnider said. "Lines are really being drawn here."
With national security heading voters' lists of concerns, "we think this is set to be the first national security election since the invasion of Iraq," Shnider said.