NNZ-2591

Also known as: Cyclo-G-2-allyl-Pro, cG-2AllylP

An oral synthetic analog of cyclic glycine-proline, an IGF-1 metabolite, in phase 3 for Phelan-McDermid syndrome. Investigational; not approved.

Last updated October 26, 2026

Mechanism of Action

NNZ-2591 is a synthetic diketopiperazine analog of cyclic glycine-proline (cGP), a small molecule formed naturally from the N-terminal end of insulin-like growth factor 1 (IGF-1). cGP is thought to help regulate how much IGF-1 is available to act on its receptor; NNZ-2591 adds an allyl group to proline to improve stability and oral bioavailability. In mouse models of several neurodevelopmental disorders it normalized synaptic and behavioral abnormalities, which is the basis for testing it in Phelan-McDermid, Angelman, Pitt-Hopkins and Prader-Willi syndromes.

Half-life: Not well established
Administration Routes: Oral
Research Status: Clinical

Reported Benefits

Open-label phase 2 trial in Phelan-McDermid syndrome reported clinician- and caregiver-rated improvements
Phase 2 open-label studies also run in Angelman, Pitt-Hopkins and Prader-Willi syndromes
Phase 3 Koala trial in Phelan-McDermid syndrome began dosing in 2026

Potential Side Effects

Generally well tolerated in phase 2 reports
Mostly mild to moderate adverse events in open-label trials
Long-term safety not established

Common Dosing

No approved dose. Trials have used an oral liquid given twice daily to children with weight-based dosing. Use is limited to clinical trials under investigator supervision.

The dosing information above is aggregated from research literature and anecdotal community reports for educational purposes only. It is not a recommendation, prescription, or medical advice. Peptides are sold as research chemicals only and are not intended for human use.

Contraindications

Investigational: not established

No documented stacking partners for NNZ-2591 yet.

NNZ-2591 in Children and Adolescents With Phelan-McDermid Syndrome: Single-Group, Open-Label, Phase 2 Trial Results
2026
Note: An erratum to this article was published in 2026 (PMID 42325945).
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NNZ-2591, a novel diketopiperazine, prevented scopolamine-induced acute memory impairment in the adult rat
2010
Note: Preclinical study in rats.
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No. As of 2026 NNZ-2591 is investigational. Neuren Pharmaceuticals began dosing its phase 3 Koala trial in children aged 3 to 12 with Phelan-McDermid syndrome in February 2026, and the program holds FDA Fast Track, Orphan Drug and Rare Pediatric Disease designations.

Both come from Neuren Pharmaceuticals and are based on small fragments of IGF-1. Trofinetide is a linear tripeptide analog approved for Rett syndrome, while NNZ-2591 is a cyclic dipeptide analog being developed for other rare neurodevelopmental disorders.