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NNZ-2591 (cyclo-L-glycyl-L-2-allylproline) is an investigational synthetic analog of cyclic glycine-proline (cGP), a breakdown product of human insulin-like growth factor 1 (IGF-1), that has been chemically modified to increase its half-life, stability, and oral bioavailability. It is currently under development by Neuren Pharmaceuticals for the symptomatic treatment of Angelman, Phelan-McDermid, and Pitt Hopkins Syndromes. It was granted Orphan Drug Designation by the FDA in October 2019 and was granted a patent by the European Patent Office in December 2019. Clinical trials are expected to begin in 2020.
NNZ-2591 (cyclo-L-glycyl-L-2-allylproline) is an investigational synthetic analog of cyclic glycine-proline (cGP), a breakdown product of human insulin-like growth factor 1 (IGF-1), that has been chemically modified to increase its half-life, stability, and oral bioavailability. It is currently under development by Neuren Pharmaceuticals for the symptomatic treatment of Angelman, Phelan-McDermid, and Pitt Hopkins Syndromes. It was granted Orphan Drug Designation by the FDA in October 2019 and was granted a patent by the European Patent Office in December 2019. Clinical trials are expected to begin in 2020.
Insulin-like growth factor 1 (IGF-1) is a hormone secreted by glia and neurons of the CNS that plays an important role in normal brain development and response to pathologies. It is broken down into two separate molecules in the brain, both of which have synthetic analogues in development. Glypromate, or GPE, comprises the last three peptides of IGF-1 and acts on glial cells, in contrast to its parent compound which tends to act on neurons - a synthetic analogue, trofinetide, is currently under development by Neuren Pharmaceuticals for the treatment of traumatic brain injury, Rett Syndrome, and Fragile X Syndrome. Glypromate is further cleaved into cyclic glycine-proline (cGP), which serves a number of diverse roles including the regulation of IGF-1 bioavailability, and of which NNZ-2591 is a synthetic analogue. While the specific actions of NNZ-2591 will likely become clearer following clinical trials, IGF-1 and its derivatives are known to facilitate brain development and normal functioning by regulating responses to disease, stress, injury through a number of signaling pathways. For this reason, any therapeutic benefit observed with NNZ-2591 is likely to be the result of many diverse effects rather than action on a specific target.
