Scientific Reference
P021
Evidence profile: Predominantly preclinical
P021 is a peptidomimetic derived from ciliary neurotrophic factor, carrying an adamantylated glycine at its C-terminus. Its originators describe a four-residue core identified by epitope mapping of the most active region of CNTF, with the adamantane-bearing residue added to increase blood-brain barrier permeability and reduce breakdown by exopeptidases. Nearly all published work comes from one group in New York, in rat and transgenic mouse models of ageing, Alzheimer-type pathology and Down syndrome. An independent 2024 study in a model of CDKL5 deficiency reported changes in cultured cells but no matching change in mice.
Mechanism of Action
The published account is indirect. P021 is described as a mimetic of a small active region of ciliary neurotrophic factor, and the reported downstream step is raised expression of brain-derived neurotrophic factor, with an associated fall in glycogen synthase kinase-3 beta activity reported in a triple-transgenic mouse model. Changes in neurogenesis and in dendritic and synaptic markers are attributed to that route. An independent 2024 study in Cdkl5 knockout mice found no rise in BDNF, so the proposed route has not been reproduced in every model tested.
Molecular Information
- Type: Peptidomimetic
- Length: 5 amino acids
- Molecular weight: 578.7 g/mol
- Molecular formula: C27H42N6O8
- CAS: 1246751-68-7