NNZ-2591
Identification
- Generic Name
- NNZ-2591
- DrugBank Accession Number
- DB15601
- Background
NNZ-2591 (cyclo-L-glycyl-L-2-allylproline)1 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.4 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 20193 and was granted a patent by the European Patent Office in December 2019.2 Clinical trials are expected to begin in 2020.3,2
- Type
- Small Molecule
- Groups
- Investigational
- Structure
- Weight
- Average: 194.234
Monoisotopic: 194.105527699 - Chemical Formula
- C10H14N2O2
- Synonyms
- Cyclo(-L-glycyl-L-2-allylproline)
- Pyrrolo(1,2-a)pyrazine-1,4-dione, hexahydro-8a-(2-propenyl)-, (8aR)-
- External IDs
- NNZ-2591
Pharmacology
- Indication
Not Available
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
Not Available
- Mechanism of action
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.4 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.4 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.4
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.4 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.4
- Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- Not Available
Categories
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 2T1HU6069S
- CAS number
- 847952-38-9
- InChI Key
- WVKCGUOWPZAROG-JTQLQIEISA-N
- InChI
- InChI=1S/C10H14N2O2/c1-2-4-10-5-3-6-12(10)8(13)7-11-9(10)14/h2H,1,3-7H2,(H,11,14)/t10-/m0/s1
- IUPAC Name
- (8aR)-8a-(prop-2-en-1-yl)-octahydropyrrolo[1,2-a]pyrazine-1,4-dione
- SMILES
- C=CC[C@@]12CCCN1C(=O)CNC2=O
References
- General References
- Guan J, Zhang R, Dale-Gandar L, Hodgkinson S, Vickers MH: NNZ-2591, a novel diketopiperazine, prevented scopolamine-induced acute memory impairment in the adult rat. Behav Brain Res. 2010 Jul 11;210(2):221-8. doi: 10.1016/j.bbr.2010.02.039. Epub 2010 Feb 25. [Article]
- EPA Insight: NNZ-2591 patent granted in Europe to 2034 for neurodevelopmental disorders [Link]
- BusinessWire: FDA Grants Orphan Drug Designation for Neuren's NNZ-2591 to Treat Angelman, Phelan-McDermid and Pitt Hopkins Syndromes [Link]
- Neuren Pharmaceuticals: Product Development [Link]
- External Links
- ChemSpider
- 9910403
- ChEMBL
- CHEMBL4802144
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 2 Active Not Recruiting Treatment Phelan McDermid Syndrome 1 2 Recruiting Treatment Angelman's syndrome 1 2 Recruiting Treatment Pitt Hopkins Syndrome 1 2 Recruiting Treatment Prader-Willi Syndrome 1 1 Completed Treatment Healthy Volunteers (HV) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Not Available
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 77.5 mg/mL ALOGPS logP -0.45 ALOGPS logP -0.27 Chemaxon logS -0.4 ALOGPS pKa (Strongest Acidic) 11.53 Chemaxon pKa (Strongest Basic) -3.7 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 49.41 Å2 Chemaxon Rotatable Bond Count 2 Chemaxon Refractivity 51.67 m3·mol-1 Chemaxon Polarizability 19.72 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0002-0900000000-5f0a2f953570ca66e503 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0006-0900000000-5b479313561887d79da4 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-03di-0900000000-f3de8b4dd4c0290a9026 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-052f-0900000000-e0c6c54bbc2d813f76f2 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-1000-0900000000-92fb7a9e49f77a3e0093 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-1003-1900000000-cca0fef6add52d3e3076 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Drug created at January 08, 2020 18:20 / Updated at May 24, 2023 10:27