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Adipotide

Emerging

Prohibitin-Targeting Peptidomimetic | Experimental Anti-Obesity

Dose 0.43 mg/kg
Frequency Once daily
Cycle 28 days
Storage Lyophilized: -20°C freezer. Reconstituted: 2-8°C refrigerated

Chimeric adipose-vasculature-targeted peptidomimetic targeting prohibitin/annexin A2 on white adipose tissue endothelium, delivering pro-apoptotic D-(KLAKLAK)2 motif. In obese primates it produced rapid fat loss with improved insulin resistance, yet development halted after Phase 1 due to kidney safety signals.

Mechanism of Action

CKGGRAKDC ligand homes to prohibitin/annexin A2 on white-fat endothelium; linked D-(KLAKLAK)2 disrupts mitochondrial membranes post-internalization, triggering localized endothelial apoptosis and adipocyte loss.

Key Benefits

  • Rapid fat-mass reduction via selective white adipose tissue vascular targeting
  • Improved insulin sensitivity following adipose reduction
  • Non-CNS peripheral mechanism distinct from appetite suppressants
Molecular Weight
N/A
Chain Length
N/A
Type
Chimeric peptidomimetic
Amino Acid Sequence
CKGGRAKDC-GG-D(KLAKLAK)2

Complex or non-standard sequence format

Weight Loss

  • Adipose Mass Reduction

    Selective white adipose tissue vascular targeting produced 7-15% body-weight loss over 4 weeks in obese macaques.

Metabolic

  • Insulin Resistance

    Improved insulin response (reduced insulin AUC) following fat-mass reduction in primates.

Appetite Control

  • Non-CNS Mechanism

    Weight loss without primary appetite suppression; peripheral vascular approach.

Rapid fat-mass reduction in obese non-human primates with improved insulin sensitivity; direct white adipose tissue vascular targeting.

GoalDoseFrequencyRoute
Primate Research Replication0.43 mg/kgOnce dailySubQ
Dose-Finding (Research)0.10-0.75 mg/kgOnce daily (escalating tiers)SubQ

Reconstitution Instructions

Materials Needed:
  • Lyophilized peptide vial
  • Bacteriostatic water (BAC water)
  • Alcohol swabs & sterile syringes
  • Insulin syringes (0.5-1 mL)
  1. 1 Sanitize hands and workspace; swab vial septum
  2. 2 Inject BAC water slowly down vial wall; do not jet onto powder
  3. 3 Gently swirl until fully dissolved (do not shake)
  4. 4 Label with concentration/date; store at 2-8°C
Semaglutide

Potential additive dehydration/GI effects; monitor renal function.

monitor
Tirzepatide

Overlapping weight-loss effects; monitor kidney function, volume status, electrolytes.

monitor
Cagrilintide

No clinical data on co-administration; mechanisms differ.

monitor
AOD-9604

No published data on combined use or pharmacodynamic interaction.

monitor
BPC-157

No known direct interaction; distinct mechanisms and targets.

compatible
CJC-1295/Ipamorelin

Metabolic effects may confound body-composition endpoints.

monitor
Melanotan II

Theoretical vascular/pressor effects; stagger dosing, monitor BP and hydration.

monitor
Nephrotoxic Drugs

Adipotide shows dose-dependent proximal tubule injury; avoid additional renal insults.

avoid
Week 1-2

Early reduction in abdominal circumference

Week 2-4

Progressive weight/fat-mass decline

Post-Discontinuation

Partial rebound possible; lab signals include mild creatinine rise and electrolyte shifts

Common Side Effects

  • Mild creatinine elevation
  • Electrolyte shifts
  • Dose-dependent proximal tubule changes (reversible in primates)

Stop Signs - Discontinue if:

  • Sustained creatinine elevation or oliguria
  • Progressive electrolyte abnormalities
  • Severe injection-site reactions or systemic symptoms
  • Unexpected toxicity

Contraindications

  • Pregnancy/lactation (not studied)
  • Dehydration
  • Concurrent nephrotoxic medications

Good Signs

  • Intact lyophilized cake - white, uniform indicates proper lyophilization
  • Clear solution - fully dissolved, particle-free after reconstitution

Warning Signs

  • Minor clumping may form from shipping; should dissolve with gentle swirl

Bad Signs

  • Collapsed/moist cake suggests temperature excursion; do not use without QC
  • Cloudiness/precipitate indicates degradation or contamination—discard
  • A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys
    (2011)

    Rhesus macaques at 0.43 mg/kg SC daily for 28 days showed 7.4-14.7% weight loss; insulin resistance improved; mild, dose-dependent, reversible proximal tubule changes.

  • Reversal of obesity by targeted ablation of adipose tissue
    (2004)

    Mice with diet-induced obesity showed ~30% weight reduction; adipose vascular apoptosis; metabolic normalization.

  • Prohibitin/Annexin A2 Interaction Regulates Fatty-Acid Transport
    (2016)

    Mechanistic validation of prohibitin/ANXA2 axis in adipose tissue, core to TP01 targeting.

  • Mixed-Chirality Prohibitin Peptide: D-(RLARLAR)2 Enhances Stability
    (2025)

    Next-generation prohibitin constructs improve serum stability and efficacy vs. first-generation TP01.

Disclaimer

This information is for educational and research purposes only. Consult a healthcare professional before use.