5-Amino-1MQ vs FOXO4-DRI

Side-by-side comparison of mechanisms, dosing, interactions, and stacking potential.

5-Amino-1MQFOXO4-DRI
CategoryPeptidesPeptides
Standard DoseResearch indicates 50-150 mg daily via oral administration, typically divided into 1-2 doses.Research indicates dosing remains experimental. Mouse studies used 5 mg/kg IV, three times weekly.
TimingMorning dosing preferred. Can be taken with or without food.No established timing protocol.
Cycle Duration8-12 week cycles.Mouse studies used intermittent dosing (3x/week for several weeks). Human protocols not established.
Evidence Levelanimal_plus_anecdotalanimal_plus_anecdotal
A

5-Amino-1MQ

Peptides

Mechanism

5-Amino-1MQ is a small molecule inhibitor of nicotinamide N-methyltransferase (NNMT), an enzyme that catalyzes the transfer of a methyl group from S-adenosylmethionine (SAM) to nicotinamide, generating 1-methylnicotinamide (1-MNA). By inhibiting NNMT, 5-Amino-1MQ increases intracellular NAD+ levels, reduces 1-MNA production, suppresses lipogenesis in adipocytes, and modulates the methionine-homocysteine cycle. In vivo, it significantly reduces body weight, white adipose mass, and adipocyte size through enhanced energy expenditure and altered lipid metabolism.

Standard Dosing

Research indicates 50-150 mg daily via oral administration, typically divided into 1-2 doses.

Timing

Morning dosing preferred. Can be taken with or without food.

Cycle Duration

8-12 week cycles.

Side Effects

  • Mild GI discomfort
  • Headache
  • Diarrhea (uncommon)
  • Nausea at higher doses

Contraindications

  • Pregnancy and breastfeeding
  • Severe hepatic impairment
  • Active cancer (NAD+ modulation concern)

Best Stacking Partners

MOTS-cAOD-9604TesofensineSemaglutide
B

FOXO4-DRI

Peptides

Mechanism

FOXO4-DRI is a D-retro-inverso peptide that selectively targets the FOXO4-p53 protein-protein interaction in senescent cells. In senescence, FOXO4 binds p53's disordered transactivation domain (TAD2) in the nucleus, preventing p53 from translocating to mitochondria where it would trigger apoptosis. FOXO4-DRI competitively disrupts this interaction, causing nuclear exclusion of p53 and its redirection to mitochondria, selectively inducing apoptosis in senescent cells while sparing healthy cells. The D-retro-inverso configuration provides protease resistance.

Standard Dosing

Research indicates dosing remains experimental. Mouse studies used 5 mg/kg IV, three times weekly.

Timing

No established timing protocol.

Cycle Duration

Mouse studies used intermittent dosing (3x/week for several weeks). Human protocols not established.

Side Effects

  • Theoretical: senolytic crisis (rapid senescent cell clearance causing inflammation)
  • Unknown long-term effects in humans
  • Potential cytokine release

Contraindications

  • Active cancer (complex interaction with p53 pathway)
  • Pregnancy and breastfeeding
  • Severe organ failure
  • Immunocompromised state

Best Stacking Partners

EpitalonGHK-CuDasatinib + Quercetin (D+Q senolytic stack)

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