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Research Comparison

FOXO4-DRI vs MOTS-C

FOXO4-DRI and MOTS-C are studied in overlapping research areas, which is why they are frequently compared. This is a neutral side-by-side reference drawn from published preclinical literature and laboratory handling data.

Shared research areas:Cellular Longevity
Class46-residue all-D retro-inverso peptideMitochondrial-derived peptide, 16 residues
Molecular weight5358.2 g/mol2174.5 g/mol
CAS number2460055-10-9Not assigned / not specified
Purity spec≥99%≥98%
Research areasCellular LongevityMetabolic, Cellular Longevity
Primary diluentSterile water (USP grade)Sterile or bacteriostatic water
Working windowCommonly worked with for 2-3 weeks at 2-8 °C in bacteriostatic water.Commonly worked with for 2–3 weeks at 2–8 °C.
Lead degradation routeDeamidation at the Asn-Gly motif in the sequence — the fastest-deamidating dipeptide in peptide chemistry.Methionine oxidation to the sulfoxide (+16 Da), and MOTS-c carries methionine at the N-terminus and internally.
Freeze–thawAliquot on first reconstitution and freeze aliquots once; avoid repeated freeze–thaw cycles, which concentrate the peptide and salts at the ice interface.Aliquot on reconstitution. Each vial opening introduces oxygen that acts on two susceptible residue types at once.
Light sensitivityContains a tryptophan residue, which is susceptible to photo-oxidation — store in the dark.Protect from light throughout — tryptophan photo-oxidation applies here as it does to DSIP.

How they actually differ

Comparing the two: FOXO4-DRI is 46-residue all-d retro-inverso peptide, while MOTS-C is mitochondrial-derived peptide, 16 residues — different molecular classes with different handling consequences; they call for different primary diluents (sterile water (usp grade) versus sterile or bacteriostatic water); their leading degradation routes differ (deamidation at the asn-gly motif in the sequence for FOXO4-DRI, methionine oxidation to the sulfoxide (+16 da), and mots-c carries methionine at the n-terminus and internally. for MOTS-C), so the storage precautions that matter are not the same; their practical working windows differ once reconstituted. The sections below set out each in full.

FOXO4-DRI — origin

FOXO4-DRI was designed in the laboratory of Peter de Keizer (Erasmus University Medical Center) and published in Cell in 2017 (Baar et al.). It mimics the region of the transcription factor FOXO4 that binds p53, but is built from D-amino acids in reversed order — a retro-inverso design that keeps the side-chain layout while making the backbone unrecognisable to proteases. A cationic, arginine-rich tail derived from the HIV-TAT cell-penetrating sequence carries it into cells.

MOTS-C — origin

MOTS-c is encoded not in nuclear DNA but within the mitochondrial genome — specifically an open reading frame inside the 12S ribosomal RNA gene. Its discovery helped establish that mitochondria encode short signalling peptides that act on the rest of the cell, a genuinely recent addition to cell biology and the reason the compound attracted rapid research interest.

FOXO4-DRI research themes

FOXO4–p53 interaction in senescent cells

The founding study showed that senescent cells rely on FOXO4 holding p53 in the nucleus. Interfering with that interaction caused p53 nuclear exclusion and intrinsic apoptosis selectively in senescent cells in culture (Baar et al., Cell 2017).

Chemotoxicity and ageing mouse models

The same study examined doxorubicin-induced senescence, fast-ageing XpdTTD/TTD mice and naturally aged mice, reporting changes in fur density, fitness and renal markers.

Senescent Leydig cells

Studied in hydrogen-peroxide-induced senescent TM3 Leydig cells and aged mice for effects on the testicular microenvironment (Zhang et al., Aging 2020).

Expanded human chondrocytes

At 25 µM in vitro it removed a large share of late-passage (senescent-enriched) human chondrocytes while sparing early-passage cells, without improving cartilage-forming capacity (Huang et al., Front Bioeng Biotechnol 2021).

MOTS-C research themes

Mitochondrial-derived signalling

Part of a novel class demonstrating that mitochondria encode peptides acting systemically.

AMPK pathway

The most-studied signalling interaction, examined in metabolic and exercise models.

Insulin sensitivity

Investigated in glucose-metabolism research models.

Exercise and longevity biology

Studies have examined MOTS-c expression in relation to physical activity and ageing in animal models.

FOXO4-DRI handling

  • Let the vial reach room temperature before opening.
  • Add diluent gently down the vial wall and swirl; do not vortex.
  • Use low-bind polypropylene rather than glass for dilutions — the cationic tail adsorbs to glass.
  • Protect solutions from light.

MOTS-C handling

  • Use amber vials or wrap in foil; treat light protection as mandatory rather than precautionary.
  • Minimise vial openings — headspace oxygen is the practical driver of oxidation.
  • Use low-bind labware for dilute working solutions.

Both third-party tested

Every Popular Peptides batch of FOXO4-DRI and MOTS-C is independently tested by HPLC and LC-MS with a published Certificate of Analysis. Enter a lot number to pull the COA for a specific vial.

Verify a batchPublished COAsHow we test

FOXO4-DRI reference

Full FOXO4-DRI reference FOXO4-DRI storage FOXO4-DRI reconstitution FOXO4-DRI calculatorFOXO4-DRI product details

MOTS-C reference

Full MOTS-C reference MOTS-C storage MOTS-C reconstitution MOTS-C calculatorMOTS-C product details

Related comparisons

5-Amino-1MQ vs FOXO4-DRI5-Amino-1MQ vs MOTS-CCagrilintide vs MOTS-CCJC-1295 (No DAC) vs MOTS-CCJC-1295 + Ipamorelin vs MOTS-CDSIP vs FOXO4-DRIDSIP vs MOTS-CEpithalon vs FOXO4-DRI

FOXO4-DRI and MOTS-C are supplied strictly as research chemicals for in-vitro laboratory and research use only. They are not intended for human or animal consumption, diagnostic, or therapeutic use. This comparison summarizes published preclinical literature and laboratory handling data; it is not medical advice, not a claim of efficacy, and not usage guidance.