Trofinetide(NNZ2566)

Cas No.:	853400-76-7
Chemical Name:	Trofinetide
Synonyms:	L-Glutamic acid, glycyl-2-methyl-L-prolyl-;Trofinetide;Glycyl-2-methyl-L-prolyl-L-glutamic acid (ACI);Daybue;Glycyl-L-2-methylprolyl-L-glutamic acid;NNZ 2566
SMILES:	C([C@@]1(CCCN1C(=O)CN)C)(=O)N[C@H](C(=O)O)CCC(=O)O
Formula:	C13H21N3O6
M.Wt:	315.322343587875
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	Trofinetide, a synthetic analogue of the endogenous N-terminus tripeptide, Glycine-Proline-Glutamate (GPE), has been shown to be neuroprotective in animal models of brain injury.
In Vivo:	Trofinetide (NNZ-2566) suppresses penetrating ballistic-like brain injury (PBBI) induced inflammatory cell infiltration at 3 days following PBBI as compare to vehicle treatment. Trofinetide treatment significantly reduces 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. Trofinetide treatment does not affect the PBBI-induced up-regulation of IL-6 expression at any time point, but does produce significant reductions in the injury-induced up-regulation of IL-1β, INF-γ, and TNF-α expression. Trofinetide treatment suppresses IL-1β expression in the injured brain hemisphere for up to 7 days post-PBBI[1]. The high doses of Trofinetide (NNZ-2566) (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 (pMCAo). All doses of Trofinetide completely suppress the delayed occurrence of NCS as compare with the vehicle-treated animals[2].
Animal Administration:	Three groups of eight rats are evaluated: vehicle/sham, vehicle/penetrating ballistic-like brain injury (PBBI), Trofinetide (NNZ-2566)/PBBI. A bolus injection of 10 mg/kg Trofinetide or 1 mL/kg saline (vehicle) is administered intravenously (IV) to each animal at 30 minutes post-PBBI surgery, immediately followed by a continuous IV infusion of Trofinetide at a rate of 3 mg/kg/h or an equal volume of vehicle for various durations (1 h, 4 h, or 12 h). Rats are subsequently euthanized and brain tissues are collected for processing at 1 h, 4 h, 12 h, 24 h, 3, and 7 days following the initiation of treatment[1].
References:	[1]. Wei HH, et al. NNZ-2566 treatment inhibits neuroinflammation and pro-inflammatory cytokine expression induced by experimental penetrating ballistic-like brain injury in rats. J Neuroinflammation. 2009 Aug 5;6:19. [2]. Lu XC, et al. NNZ-2566, a glypromate analog, attenuates brain ischemia-induced non-convulsive seizures in rats. J Cereb Blood Flow Metab. 2009 Dec;29(12):1924-32.