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

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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
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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
  1. 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]
  2. EPA Insight: NNZ-2591 patent granted in Europe to 2034 for neurodevelopmental disorders [Link]
  3. BusinessWire: FDA Grants Orphan Drug Designation for Neuren's NNZ-2591 to Treat Angelman, Phelan-McDermid and Pitt Hopkins Syndromes [Link]
  4. Neuren Pharmaceuticals: Product Development [Link]
ChemSpider
9910403
ChEMBL
CHEMBL4802144

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2Active Not RecruitingTreatmentPhelan McDermid Syndrome1
2RecruitingTreatmentAngelman's syndrome1
2RecruitingTreatmentPitt Hopkins Syndrome1
2RecruitingTreatmentPrader-Willi Syndrome1
1CompletedTreatmentHealthy Subjects (HS)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
PropertyValueSource
Water Solubility77.5 mg/mLALOGPS
logP-0.45ALOGPS
logP-0.27Chemaxon
logS-0.4ALOGPS
pKa (Strongest Acidic)11.53Chemaxon
pKa (Strongest Basic)-3.7Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count2Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area49.41 Å2Chemaxon
Rotatable Bond Count2Chemaxon
Refractivity51.67 m3·mol-1Chemaxon
Polarizability19.72 Å3Chemaxon
Number of Rings2Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0002-0900000000-5f0a2f953570ca66e503
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-0900000000-5b479313561887d79da4
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-03di-0900000000-f3de8b4dd4c0290a9026
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-052f-0900000000-e0c6c54bbc2d813f76f2
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-1000-0900000000-92fb7a9e49f77a3e0093
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-1003-1900000000-cca0fef6add52d3e3076
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
Not Available

Drug created at January 08, 2020 18:20 / Updated at May 24, 2023 10:27