Side-by-side · Research reference

CJC-1295 (no DAC)vsPNC-27

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

APhase 1HUMAN-REVIEWED15/51 cited

BAnimal-StrongHUMAN-REVIEWED18/41 cited

CJC-1295 (no DAC)

Short-acting GHRH · No DAC variant

100 mcgPer doseTeichman 2006

~30 minHalf-lifeIonescu 2006

Phase 1Evidence levelTeichman 2006 Sigalos 2018

SQ · Pre-sleep · 1–2×/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

CJC-1295 (no DAC)

PNC-27

Primary target

Pituitary GHRH receptorTeichman 2006

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

Pathway

GHRH-R → Gαs → cAMP → PKA → GH vesicle exocytosisTeichman 2006

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

Downstream effect

Pulsatile GH release matching physiological pattern; subsequent IGF-1 elevationIonescu 2006

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

Feedback intact?

Yes — short pulse preserves somatostatin negative feedbackIonescu 2006

N/A — cytotoxic mechanism, not signaling modulation

Origin

Modified human GRF 1-29 with four substitutions (D-Ala²/Gln⁸/Ala¹⁵/Leu²⁷) for protease resistanceTeichman 2006

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

Antibody development

Not reported in short-term studies

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02Dosage Protocols

Parameter

CJC-1295 (no DAC)

PNC-27

Standard dose

100 mcg per injectionTeichman 2006

Often paired with ipamorelin in same syringe.

—

Frequency

1–2× daily (pre-sleep ± morning)

—

Lower / starter dose

50 mcg per dose

—

Evidence basis

Phase 1 (CJC-1295 with DAC); analog dataTeichman 2006 Ionescu 2006

No-DAC variant is less studied directly; PK extrapolated from native GHRH.

Pre-clinical / In vitro

Duration

8–12 weeks on / 4 off (anecdotal)

—

Reconstitution

Bacteriostatic water

—

Timing

Pre-sleep + fasted preferred

—

Half-life

~30 minIonescu 2006

Short pulse vs CJC-1295-DAC (~8 days). Choose no-DAC for pulsatile, DAC for sustained.

—

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

CJC-1295 (no DAC)

PNC-27

Fat loss mechanism

—

None — cytotoxic anticancer agent

04Side Effects & Safety

Parameter

CJC-1295 (no DAC)

PNC-27

Injection site reaction

Erythema, mild pruritus

—

Flushing / headache

Common transient effect

—

Cortisol elevation

Minimal at standard doses

—

Prolactin elevation

Minimal

—

Glucose intolerance

Possible at high cumulative doses

—

IGF-1 elevation

Dose-dependent; monitor with chronic 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

CJC-1295 (no DAC)

·Active malignancy or cancer history
·Pregnancy / breastfeeding
·Disrupted hypothalamic-pituitary axis

PNC-27

·Human use — no clinical trials or safety data

Relative Contraindications

CJC-1295 (no DAC)

·Untreated diabetes
·Severe insulin resistance

PNC-27

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05Administration Protocol

Parameter

CJC-1295 (no DAC)

PNC-27

1. Reconstitution

Add 2 mL bacteriostatic water to 2 mg vial → 1 mg/mL = 100 mcg per 0.1 mL. Roll gently.

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

Subcutaneous, 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 preferred. Often combined with ipamorelin in the same syringe.

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, protected from light. Reconstituted: refrigerate 2–8 °C, use within 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.

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06Stack Synergy

CJC-1295 (no DAC)

+ Ipamorelin

Strong

View Ipamorelin →

CJC-1295 (no DAC) and ipamorelin are the canonical "GHRH + GHRP" dual-axis stack at physiological timing. Both peak within 30 min and clear within 2 hours, producing a sharp, high-amplitude GH pulse closely resembling natural physiology. Preferred over the CJC-1295-DAC + ipamorelin stack when pulsatility (vs sustained elevation) is the goal.

CJC-1295 (no DAC): 100 mcg SQ · pre-sleep
Ipamorelin: 200–300 mcg SQ · same injection
Primary benefit: Pulsatile GH stimulation, recovery, body composition

Teichman 2006 Raun 1998

PNC-27

— no documented stacks