P021
P021, a peptide. A ciliary-neurotrophic-factor peptide mimetic: the most active region of CNTF was located by epitope mapping, and an adamantylated glycine was added…
A ciliary-neurotrophic-factor peptide mimetic: the most active region of CNTF was located by epitope mapping, and an adamantylated glycine was added at the C-terminus to raise blood-brain-barrier permeability and blunt exopeptidase degradation. It enhances dentate-gyrus neurogenesis by inhibiting leukemia inhibitory factor signalling and increasing BDNF expression, and through that BDNF increase it lowers GSK-3-beta activity, which is the major tau kinase — so one compound acts on both the neurogenic and the tau arms of Alzheimer pathology. All efficacy is preclinical, largely in 3xTg-AD mice and aged rats fed the compound in the diet.
PubChem CID 56599151 (C27H42N6O8), CAS 1246751-68-7. Sequence Ac-DGGL(A)G-NH2, where (A) is the adamantylated glycine; the same group writes it Ac-DGGLAG-NH2 elsewhere, and PMID:28655344 calls it a "tetra-peptide" while printing six residues — RECORD THE SEQUENCE, NOT THE RESIDUE COUNT. Derivation verbatim from PMID:28655344: "Peptide 021 (P021) is a neurotrophic/neurogenic tetra-peptide that was derived from the most active region of the ciliary neurotrophic factor (CNTF) by epitope mapping. Admantylated glycine was added to its C-terminal to increase its blood-brain barrier permeability and decrease its degradation by exopeptidases to make it druggable." Brain penetration is asserted with evidence but no number (PMID:26401692, rat): "we show that P021 is blood-brain-barrier-permeable, and chronic oral treatment with this compound can reduce the brain level of total tau in the aged rats", plus "P021 does not induce any detectable immune reaction in rats". DOSING IS ROUTE AND DURATION ONLY across the whole literature — "treated for 12months with P021 or vehicle diet starting at 9-10months of age" (PMID:25046994), a diet-administered course from 3 to 21 months of age (PMID:28655344), "from prenatal day 8 to postnatal day 21 with a custom-made diet containing P021" (PMID:32854771) — so the dose block is empty rather than guessed. NAMING TRAP: PMID:27885969 is a Critical Care supplement where "P021" is an ABSTRACT NUMBER, which is why a PK search on the token returns one more hit than it should.
Sources: PMID:27400746, PMID:28655344, PMID:26401692, PMID:25046994