Trofinetide: a pioneering treatment for Rett syndrome

Trends Pharmacol Sci. 2023 Oct;44(10):740-741. doi: 10.1016/j.tips.2023.06.008. Epub 2023 Jul 16.

Abstract

STRUCTURE: Trofinetide ((2S)-2-{[(2S)-1-(2-aminoacetyl)-2-methylpyrrolidine-2-carbonyl]amino}pentanedioic acid) is derived from the tripeptide glycine-proline-glutamic acid (GPE), which is an endogenous tripeptide of the N-terminal domain of Insulin-like Growth Factor 1 (IGF-1). The compound differs from endogenous GPE by a methyl (-CH3) substitution at the α-carbon of the proline residue. This methyl substitution assists in resistance to protease cleavage and improves oral bioavailability. The molecular formula of trofinetide is C13H21N3O6, and the molecular weight is 315.33 g/mol.

Trial registration: ClinicalTrials.gov NCT02715115 NCT01703533 NCT04181723 NCT04279314 NCT04776746 NCT04988867.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Glutamates
  • Humans
  • Rett Syndrome* / drug therapy

Substances

  • trofinetide
  • Glutamates

Associated data

  • ClinicalTrials.gov/NCT02715115
  • ClinicalTrials.gov/NCT01703533
  • ClinicalTrials.gov/NCT04181723
  • ClinicalTrials.gov/NCT04279314
  • ClinicalTrials.gov/NCT04776746
  • ClinicalTrials.gov/NCT04988867