Trofinetide (NNZ-2566) is a synthetic analog of the endogenous N-terminus tripeptide. It has been shown to be neuroprotective in animal models of brain injury.

Trofinetide treatment suppresses IL-1β expression in the injured brain hemisphere for up to 7 days post-PBBI. Trofinetide suppresses penetrating ballistic-like brain injury-induced inflammatory cell infiltration at 3 days following PBBI as compared to vehicle treatment. All doses of Trofinetide completely suppress the delayed occurrence of NCS as compare with the vehicle-treated animals. Trofinetide treatment produces significant reductions in the injury-induced up-regulation of IL-1β, INF-γ, and TNF-α expression. Trofinetide treatment significantly decreases the elevation of IL-6 (79%), E-selectin (81%), IL-1β (76%), and TNF-α (72%) mRNA levels in the injured hemisphere at 12 h post-PBBI, with maximal inhibition occurring between 12 h and 24 h. The high doses of Trofinetide (10 and 100 mg/kg bolus followed by continuous infusion) attenuate non-convulsive seizure (NCS) occurring beyond 2 h after permanent middle cerebral artery occlusion [1][2].