FOXO4-DRI vs. Lixisenatide

Category

Research other

Metabolic

CAS no.

2074706-72-8

320367-13-3

Molecular weight

3735 g/mol

4858.5 g/mol

Half-life

0.5 h

3 h

Sequence

FOXO4-DRI

FOXO4-DRI is the D-retro-inverso variant of a peptide fragment of the FOXO4 transcription factor. In senescent cells, FOXO4 is bound to p53, which suppresses p53-mediated apoptosis — the cells survive in a secreting 'zombie-like' state (senescence-associated secretory phenotype, SASP). The DRI peptide disrupts this FOXO4-p53 binding, freeing p53, and the senescent cell initiates apoptosis. Healthy cells are largely unaffected because p53 is not held back by FOXO4 in them. This selectivity was the central finding of the original 2017 publication.

Lixisenatide

Lixisenatide is a 44-amino-acid peptide based on exendin-4 (see exenatide) with six additional lysine residues at the C-terminus. This modification increases stability against DPP-4 degradation. The short half-life (~3 hours) and plasma peak around mealtime explain the predominantly prandial effect — stronger postprandial glucose action, weaker fasting glucose effect than weekly GLP-1 RAs.

Highest evidence

Studies

3

5

of which in humans

0

5

Effects recorded

3

3

Open conflicts

1

1

Documented adverse events

1

1