Side-by-side · Research reference

HexarelinvsPNC-27

Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.

APhase 1HUMAN-REVIEWED19/45 cited

BAnimal-StrongHUMAN-REVIEWED18/41 cited

Hexarelin

Hexapeptide GHRP · Cardio-tropic

100–200 mcgPer doseSmith 1996

Phase 1Evidence levelGhigo 1997

~70 minHalf-lifeSemenistaya 2010

SQ · Multiple sites · 1–3×/day

PNC-27

p53-HDM-2 Peptide · Membrane-Targeting

32 AAPeptide lengthSarafraz-Yazdi 2022

12-26p53 domain

Pre-clinicalDevelopment stage

In vitro / Pre-clinical only

01Mechanism of Action

Parameter

Hexarelin

PNC-27

Primary target

Ghrelin receptor (GHS-R1a) + cardiac CD36Smith 1996 Ghigo 1997

Membrane-bound HDM-2 protein on cancer cell surfaceSarafraz-Yazdi 2022 Krzesaj 2024

Pathway

GHS-R1a → Gαq → Ca²⁺ → GH release. CD36 engagement → direct cardio-tropic actionGhigo 1997

PNC-27 binds to membrane HDM-2 1-109 domain → transmembrane pore formation → rapid necrosis (poptosis)Pincus 2024 Krzesaj 2024

Downstream effect

Strong GH pulse + IGF-1 elevation; cardio-protective effects in animal MI modelsGhigo 1997

Immediate cell lysis and extrusion of intracellular contents; secondary mitochondrial membrane disruptionPincus 2024 Krzesaj 2024

Feedback intact?

Yes initially; tachyphylaxis with chronic useGhigo 1997

N/A — cytotoxic mechanism, not signaling modulation

Origin

Synthetic hexapeptide His-D-2-Methyl-Trp-Ala-Trp-D-Phe-Lys-NH₂Smith 1996

Chimeric design: p53 transactivating domain (12-26) fused to penetratin CPP sequenceSarafraz-Yazdi 2022

Antibody development

—

02Dosage Protocols

Parameter

Hexarelin

PNC-27

Standard dose

100–200 mcg per injectionSmith 1996

—

Frequency

1–2× per day max (tachyphylaxis with chronic 3× daily)

—

Lower / starter dose

50 mcg per dose

—

Evidence basis

Phase 1 / Phase 2 trialsSmith 1996 Ghigo 1997

Pre-clinical / In vitro

Duration

4–8 weeks on / 4–8 weeks off (tachyphylaxis mitigation)

—

Reconstitution

Bacteriostatic water

—

Timing

Pre-sleep + fasted preferred

—

Half-life

~70 minSemenistaya 2010

—

Clinical status

—

Pre-clinical only — no human trials

In vitro and animal model data only.

In vitro concentrations

—

10–100 μM range

Effective concentrations in cell culture studies.

Shorter analogue

—

PNC-28 (28 AA variant)

Retains HDM-2 binding and cytotoxic activity.

03Metabolic / Fat Loss Evidence

Parameter

Hexarelin

PNC-27

Fat loss mechanism

—

None — cytotoxic anticancer agent

04Side Effects & Safety

Parameter

Hexarelin

PNC-27

Cortisol elevation

Modest at high dosesGhigo 1997

—

Prolactin elevation

Modest at high dosesGhigo 1997

—

Hunger

Strong appetite increase via ghrelin agonism

—

Tachyphylaxis

Receptor desensitisation with chronic dosingGhigo 1997

—

Cardiac effects

Direct cardio-tropic; potential benefit in MI but unstudied in humansGhigo 1997

—

IGF-1 elevation

Strong; monitor with chronic high-dose use

—

Cancer risk

Contraindicated in active malignancy (GH/IGF-1 axis)

—

Pregnancy / OB

Avoid

—

Human safety data

—

None available — no human trials conducted

Normal cell selectivity

—

In vitro: no cytotoxicity to normal cells (MCF-10-2A, peripheral blood mononuclear cells)Sarafraz-Yazdi 2010 Thadi 2020

Normal cells express minimal membrane HDM-2.

Cancer cell specificity

—

Depends on membrane HDM-2 expression levels

Ovarian cancer lines with low membrane HDM-2 showed <30% necrosis.

Cell death mechanism

—

Necrosis (not apoptosis) — rapid membrane lysisPincus 2024

Mitochondrial effects

—

Secondary mitochondrial membrane disruption in cancer cells

Absolute Contraindications

Hexarelin

·Active malignancy
·Pregnancy / breastfeeding
·Disrupted hypothalamic-pituitary axis

PNC-27

·Human use — no clinical trials or safety data

Relative Contraindications

Hexarelin

·Untreated diabetes
·Severe hyperprolactinemia

PNC-27

—

05Administration Protocol

Parameter

Hexarelin

PNC-27

1. Reconstitution

Add 2 mL bacteriostatic water to 5 mg vial → 2.5 mg/mL = 250 mcg per 0.1 mL.

PNC-27 has not been tested in human subjects. All data derive from in vitro cancer cell line studies and limited animal models. No approved clinical formulation, dosing protocol, or safety profile exists.Pincus 2024

2. Injection site

SQ — abdomen or thigh. Rotate sites.

In vitro studies used 10–100 μM PNC-27 dissolved in cell culture medium. Peptide was added directly to cancer cell cultures (pancreatic, breast, colon, ovarian, leukemia lines) and incubated for 24–72 hours.

3. Timing

Pre-sleep + fasted preferred. Cycle on/off to avoid tachyphylaxis.

Dual-labeled PNC-27 (green on N-terminus, red on C-terminus) demonstrated intact peptide binding to cancer cell membranes with combined yellow fluorescence at 30 minutes, persisting during cell lysis.Sookraj 2010

4. Storage

Lyophilised: room temp, light-protected. Reconstituted: refrigerate ≤30 days.

Cytotoxicity correlates directly with membrane HDM-2 expression levels. Blocking HDM-2's p53-binding domain (1-109) with monoclonal antibodies prevents PNC-27-induced necrosis.

5. Needle

29–31G, 4–8 mm insulin syringe.

—

06Stack Synergy

Hexarelin

+ CJC-1295 (no DAC)

Strong

View CJC-1295 (no DAC) →

Hexarelin (GHRP) + CJC-1295-no-DAC (GHRH analogue) is the higher-amplitude variant of the standard GHRH+GHRP stack. Hexarelin produces a stronger pulse than ipamorelin but with cortisol + prolactin signal — choose this stack for maximum GH amplitude when side-effect tolerance is acceptable. Cycle aggressively.

Hexarelin: 100 mcg SQ · pre-sleep
CJC-1295 (no DAC): 100 mcg SQ · same injection
Primary benefit: Maximum GH pulse amplitude (with side-effect signal)

Smith 1996 Teichman 2006

PNC-27

— no documented stacks