Cell-killing peptides
These three peptides are designed to make particular cells die: PNC-27 cancer cells, adipotide the blood vessels that feed white fat, and FOXO4-DRI worn-out (senescent) cells. All rest on cell and animal studies, since adipotide’s only human trial was stopped after four patients without reporting results and the other two have never been given to a person, yet all three are sold as research chemicals.
- Compounds
- 3
- Approved drug
- 0
- Human studies
- 0
- Preclinical
- 3
Members
Aimed at cancer cells
A piece of p53 joined to a membrane-seeking tail. It binds HDM-2, which many cancer cells carry in their outer membrane, and is said to punch holes there; cell and mouse data only.
| Compound | What it is | Approval | Evidence | How often | Half-life | Sport |
|---|---|---|---|---|---|---|
| PNC-27 | Experimental anticancer peptide | Not approved | Preclinical | Not established | Not measured | Likely banned |
Aimed at fat’s blood vessels
A loop that homes to prohibitin on the lining of blood vessels feeding white fat, joined to a membrane-disrupting tail. Also covered with the other weight-loss compounds.
| Compound | What it is | Approval | Evidence | How often | Half-life | Sport |
|---|---|---|---|---|---|---|
| Adipotide | Fat-vessel-killing peptide (experimental) | Not approved | Preclinical | Not established | Not measured | Likely banned |
Aimed at worn-out (senescent) cells
A mirror-image peptide that breaks the FOXO4–p53 bond keeping senescent cells alive, so they self-destruct. Also covered with the mitochondrial and longevity peptides.
| Compound | What it is | Approval | Evidence | How often | Half-life | Sport |
|---|---|---|---|---|---|---|
| FOXO4-DRI | Experimental senolytic peptide | Not approved | Preclinical | Not established | Not measured | Likely banned |
Approval, evidence, half-life and sport status restate each compound’s own page, where the sources are listed. Select a name for doses, side effects and studies.
How they work
Most peptides on this site nudge a signal: they switch a receptor on or off, and the cell carries on. These three are built to make chosen cells die. Each pairs a part meant to find one kind of cell with a part that kills it, or that removes what keeps it alive. If the targeting works, the unwanted cells go and the rest are spared; if it slips, the same chemistry harms healthy tissue. How well each tells its targets from healthy cells is therefore the central safety question, and in people it has never been tested. Precaution
PNC-27 carries the stretch of p53 that grips HDM-2, joined to a sequence that pulls it into membranes. Many cancer cells carry HDM-2 in their outer membrane, which normal cells largely don’t, and there the peptide is said to build pores that let the cell’s contents leak out; an independent 2020 study credited the breakdown of E-cadherin, a cell-surface protein, instead. Adipotide’s loop sticks to prohibitin on vessel-lining cells in white fat, and its mirror-image tail breaks up the mitochondria of the cell it enters. FOXO4-DRI frees p53 inside senescent cells, which then self-destruct. Animal
In animals the targeting mostly held, at a cost. PNC-27 killed many cancer cell lines but not normal cells in culture, and slowed human pancreatic tumors and leukemia in mice. Obese monkeys given adipotide daily for four weeks lost 7.4–14.7% of body weight, though they also ate less, and their kidney tubules were injured, more so at higher doses; most of that reversed within 28 days of stopping. FOXO4-DRI improved fitness, fur density and kidney function in old mice, but clearing senescent cells with it or another senolytic raised lung blood pressure in later mouse work. Animal
No one has shown that any of the three works, or is tolerated, in people. Adipotide’s only trial, a first-in-human study at a US cancer center in men with metastatic prostate cancer and obesity, started in 2012, enrolled 4 of up to 15 planned patients and was terminated at the investigator’s request; it closed in January 2019 with no results posted or published. PNC-27 and FOXO4-DRI have no published human study and no registered trial (ClinicalTrials.gov, October 2026). PNC-27’s work on cells taken from patients was done in a dish, not in people. Trial
How they differ
What each targets
AnimalPNC-27: HDM-2 in the outer membrane of many cancer cells. Adipotide: prohibitin on the lining of blood vessels that feed white fat, so fat is starved of blood rather than attacked directly. FOXO4-DRI: the FOXO4–p53 bond inside senescent cells.
How the cell dies
AnimalPNC-27 is said to burst cells through membrane pores, though a 2020 study proposed E-cadherin breakdown instead. Adipotide’s tail breaks up the mitochondria of the vessel cells it enters. FOXO4-DRI lets p53 trigger apoptosis, the cell’s own orderly self-destruction.
How far each got
Adipotide reached one first-in-human trial, terminated after 4 patients with nothing reported, and no later trial is registered. PNC-27 has stayed in the lab since the 2000s, with a company involved in recent years. FOXO4-DRI has cell and mouse work only and is not in clinical development.
Who did the work
Most PNC-27 work comes from the New York laboratory that designed it and its collaborators, with one independent cancer-center study. Adipotide’s data come from its developers, and a 2012 letter argued the monkeys lost weight mainly by eating less. FOXO4-DRI rests on one 2017 paper and later mouse studies.
History
- 2004A team at MD Anderson Cancer Center reported a peptide loop that binds prohibitin on the blood vessels of white fat; joined to a cell-killing tail, it reversed obesity in mice.
- 2010PNC-27 was reported to bind HDM-2 in cancer-cell membranes and kill those cells by forming pores, leaving normal cells intact in culture.
- 2011Adipotide cut weight and body fat in obese monkeys over four weeks, with kidney damage that grew with dose and mostly reversed after stopping.
- 2012Adipotide’s first-in-human trial opened in men with metastatic prostate cancer and obesity; it was later terminated after 4 patients, with no results ever posted.
- 2017FOXO4-DRI was reported to clear senescent cells in mice, blunting chemotherapy damage and improving fitness, fur density and kidney function in old animals.
Comparisons and guides
Questions
What are cell-killing peptides?
Peptides designed to make one kind of cell die, rather than to switch a signal on or off. PNC-27 targets cancer cells, adipotide the blood vessels that feed white fat, and FOXO4-DRI worn-out (senescent) cells. Each pairs a targeting part with a killing part, and all three rest on cell and animal studies only.
Is PNC-27 a cancer treatment?
No. It killed many cancer cell lines in culture and slowed human pancreatic tumors and leukemia in mice, mostly in work from the laboratory that designed it. No person has been given it in a published study and no trial is registered. Its page warns against using it in place of, or alongside, real cancer treatment.
Does adipotide cause weight loss in people?
No one knows. Obese monkeys lost 7.4–14.7% of their weight in four weeks, but they also ate less, and their kidneys were injured. The only human trial, in men with metastatic prostate cancer and obesity, enrolled 4 patients, was terminated at the investigator’s request and never reported weight, safety or anything else.
Has anyone taken FOXO4-DRI?
Not in any published study, and no trial is registered. Its evidence is a 2017 mouse paper and later mouse work. How long it lasts in the body has never been measured, and senescent cells help wounds heal and stop damaged cells dividing, so what clearing them does in a person is unknown.
Are cell-killing peptides banned in sport?
Likely, yes. WADA’s 2026 list doesn’t name PNC-27, adipotide or FOXO4-DRI, but none is approved by any health authority, so all three fall under S0, non-approved substances, banned at all times.
Sources
- Sarafraz-Yazdi et al., PNC-27 binds HDM-2 in cancer cell membranes and kills those cells (Proc Natl Acad Sci U S A 2010) PMID 20080680
- Sarafraz-Yazdi et al., imaging of the pores PNC-27 forms, and neither half killing cells alone (Biomedicines 2022) PMID 35625682
- Wang et al., membrane HDM2 in acute myeloid leukemia, with PNC-27 killing through E-cadherin breakdown in mice (Leukemia 2020) PMID 31337857
- Kolonin et al., reversal of obesity by targeted ablation of fat tissue, the prohibitin-binding loop (Nat Med 2004) PMID 15133506
- Barnhart et al., adipotide in obese Old World monkeys: weight loss and reversible kidney changes (Sci Transl Med 2011) PMID 22072637
- Criscione, letter arguing the monkey weight loss reflected reduced food intake (Sci Transl Med 2012) PMID 22539771
- ClinicalTrials.gov record of the first-in-human trial of Prohibitin-TP01 (adipotide): terminated, 4 enrolled, no results posted (checked October 8, 2026) NCT01262664
- Baar et al., targeted apoptosis of senescent cells restores tissue homeostasis (Cell 2017) PMID 28340339
- Bourgeois et al., FOXO4-DRI binds the disordered p53 transactivation domain (Nat Commun 2025) PMID 40593617
- Born et al., eliminating senescent cells, including with FOXO4-DRI, can promote pulmonary hypertension in mice (Circulation 2023) PMID 36515093
Each compound’s page lists the sources for its own doses, status and studies.