BEIRUT—Syrian rebels pierced the innermost circle of President Bashar al-Assad's regime with a bomb blast that killed three high-level officials and raised questions about the ability of the country's security forces to sustain the embattled government.

Wednesday's explosion, coming after days of pitched battles in the capital of Damascus, came as a huge blow to the Assad regime, highlighting its growing vulnerability while showing the increasing ability of rebels in the 17-month uprising. But analysts said it likely didn't mark a decisive turning point for rebels, who remain outgunned by the Russian-backed Syrian military.

U.S. officials said the developments in Syria showed Mr. Assad was losing control of the country, and said it was urgent that the international community increase pressure for him to step down.

A United Nations Security Council vote on the future of a moribund peacekeeping mission, which expires Friday, was postponed until Thursday. With Russia seen as a significant obstacle to Security Council action, President Barack Obama called Russian President Vladimir Putin; the two acknowledged differences over the issue of sanctions against Damascus, the White House said.

The bombing on Wednesday targeted a meeting of military, security and intelligence leaders that Syrian officials call a "crisis cell," a committee that has met regularly in recent months as the crisis escalated, according to Syrian Information Minister Omran al-Zughbi. Among those killed were Mr. Assad's brother-in-law and the Syrian defense minister.