trofinetide   Click here for help

GtoPdb Ligand ID: 12482

Synonyms: ACP-2566 | analogue 4 [PMID: 15837309] | Daybue® | glycyl-alpha-methyl-L-prolyl-L-glutamic acid | NNZ-2566 | NNZ2566
Approved drug
trofinetide is an approved drug (FDA (2023))
Compound class: Peptide or derivative
Comment: Trofinetide (NNZ-2566), a synthetic analogue of the amino‐terminal tripeptide of insulin-like growth factor 1 (IGF-1; GPE). It was developed as a neuroprotective agent, for potential application in neurodegenerative diseases of the central nervous system, and traumatic brain injury.
The endogenous glycine-proline-glutamate tripeptide (GPE, Glypromate) is present in the brain [7], and it has been demonstrated to partially reverse core symptoms in Mecp2-deficient mice that are a model of human Rett syndrome [8]. Trofinetide has been modified to offer a longer half-life than GPE.
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES C[C@]1(CCCN1C(=O)CN)C(=O)N[C@@H](CCC(=O)O)C(=O)O
Isomeric SMILES C[C@]1(CCCN1C(=O)CN)C(=O)N[C@@H](CCC(=O)O)C(=O)O
InChI InChI=1S/C13H21N3O6/c1-13(5-2-6-16(13)9(17)7-14)12(22)15-8(11(20)21)3-4-10(18)19/h8H,2-7,14H2,1H3,(H,15,22)(H,18,19)(H,20,21)/t8-,13-/m0/s1
InChI Key BUSXWGRAOZQTEY-SDBXPKJASA-N
References
1. Alonso De Diego SA, Muñoz P, González-Muñiz R, Herranz R, Martín-Martínez M, Cenarruzabeitia E, Frechilla D, Del Río J, Jimeno ML, García-López MT. (2005)
Analogues of the neuroprotective tripeptide Gly-Pro-Glu (GPE): synthesis and structure-activity relationships.
Bioorg Med Chem Lett, 15 (9): 2279-83. [PMID:15837309]
2. Berry-Kravis E, Horrigan JP, Tartaglia N, Hagerman R, Kolevzon A, Erickson CA, Hatti S, Snape M, Yaroshinsky A, Stoms G et al.. (2020)
A Double-Blind, Randomized, Placebo-Controlled Clinical Study of Trofinetide in the Treatment of Fragile X Syndrome.
Pediatr Neurol, 110: 30-41. [PMID:32660869]
3. Glaze DG, Neul JL, Kaufmann WE, Berry-Kravis E, Condon S, Stoms G, Oosterholt S, Della Pasqua O, Glass L, Jones NE et al.. (2019)
Double-blind, randomized, placebo-controlled study of trofinetide in pediatric Rett syndrome.
Neurology, 92 (16): e1912-e1925. [PMID:30918097]
4. Keam SJ. (2023)
Trofinetide: First Approval.
Drugs, 83 (9): 819-824. [PMID:37191913]
5. Neul JL, Percy AK, Benke TA, Berry-Kravis EM, Glaze DG, Peters SU, Jones NE, Youakim JM. (2022)
Design and outcome measures of LAVENDER, a phase 3 study of trofinetide for Rett syndrome.
Contemp Clin Trials, 114: 106704. [PMID:35149233]
6. Percy AK. (2016)
Progress in Rett Syndrome: from discovery to clinical trials.
Wien Med Wochenschr, 166 (11-12): 325-32. [PMID:27491553]
7. Silva-Reis SC, Sampaio-Dias IE, Costa VM, Correia XC, Costa-Almeida HF, García-Mera X, Rodríguez-Borges JE. (2023)
Concise Overview of Glypromate Neuropeptide Research: From Chemistry to Pharmacological Applications in Neurosciences.
ACS Chem Neurosci, 14 (4): 554-572. [PMID:36735764]
8. Tropea D, Giacometti E, Wilson NR, Beard C, McCurry C, Fu DD, Flannery R, Jaenisch R, Sur M. (2009)
Partial reversal of Rett Syndrome-like symptoms in MeCP2 mutant mice.
Proc Natl Acad Sci U S A, 106 (6): 2029-34. [PMID:19208815]