reviewed april 2026|next review october 2026|88 physicians psi has verified|40749 published studies
p28 (Azurin Peptide Fragment)
p28 is a 28-amino acid peptide fragment of azurin (a bacterial protein from Pseudomonas aeruginosa) that selectively enters cancer cells and stabilizes the p53 tumor suppressor protein, with Phase I clinical trial data showing favorable safety and disease stabilization in refractory solid tumors and pediatric CNS tumors.
Evidence landscape: 40749 published studies
Published studies cover selective entry mechanism, p53 stabilization, and Phase I clinical data. The evidence base is focused but limited in volume.
- 3 Human
- 157 Animal
- 40 Reviews
- 40549 Other research
p28 preferentially enters cancer cells over normal cells through caveolae-mediated endocytosis. This selectivity is a key advantage for a cancer-directed peptide.
Adult Phase I trial showed no dose-limiting toxicities. Maximum tolerated dose was not reached. Tumor stabilization observed. Pediatric Phase I in CNS tumors also showed favorable safety.
Phase I completed. Phase II progression has not been publicly reported. The clinical development trajectory is uncertain.
PSI Assessment
p28 is one of the few peptides to complete a Phase I cancer trial with favorable results. Derived from a bacterial protein called azurin, it selectively enters cancer cells and stabilizes p53, the tumor suppressor protein that cancer cells frequently inactivate. The Phase I trial showed no dose-limiting toxicities at any dose level, the maximum tolerated dose was not reached, and tumor stabilization was observed in some patients with refractory solid tumors. A pediatric Phase I study in CNS tumors also showed favorable safety. The mechanism is well-characterized and the selectivity for cancer cells is documented. The open question is why clinical development has not visibly advanced beyond Phase I.
Selectively enters cancer cells. Stabilizes p53 tumor suppressor. Phase I showed no dose-limiting toxicities and tumor stabilization. Phase II status is unclear.
p28 enters cancer cells through caveolae-mediated endocytosis, a pathway that is more active in cancer cells than normal cells. Once inside, it binds to the N-terminal domain of p53 and prevents ubiquitination by HDM2 and COP1, the proteins that normally tag p53 for destruction. This stabilizes p53, restoring its ability to activate cell cycle arrest and apoptosis in cancer cells. The selective entry mechanism combined with the p53 stabilization mechanism makes p28 theoretically well-suited as a targeted cancer peptide. The practical question is whether disease stabilization (observed in Phase I) translates to objective tumor responses in later-phase trials.
What the evidence supports
p28 selectively enters cancer cells through caveolae-mediated endocytosis. It stabilizes p53 by preventing HDM2-mediated degradation. A Phase I clinical trial showed no dose-limiting toxicities, and the maximum tolerated dose was not reached. Tumor stabilization was observed in patients with refractory solid tumors. A pediatric Phase I study also showed favorable safety in CNS tumors.
What is not yet established
Whether p28 produces objective tumor responses (shrinkage) in humans. Efficacy as monotherapy versus combination use. The optimal patient population and cancer types most likely to respond. Why clinical development has not visibly advanced beyond Phase I.
Research Evidence
The findings below cover the selective cancer cell entry mechanism, the p53 stabilization data, and the Phase I clinical results.
Evidence by condition
Evidence dimensions for p28. Mechanism and cancer cell selectivity are well-characterized. Clinical efficacy data is limited to Phase I observations.
| Condition | Mechanism | Animal evidence | Human evidence | Replication |
|---|---|---|---|---|
| Cancer Therapy | ||||
| p53 Reactivation |
p28 preferentially enters cancer cells over normal cells through caveolae-mediated endocytosis. The selectivity has been demonstrated across multiple cancer cell types.
Selective cancer cell entry is a significant advantage. Many cancer-directed agents lack this selectivity, which limits their therapeutic window.
Inside cancer cells, p28 binds the N-terminal domain of p53 and prevents ubiquitination by HDM2. This stabilizes p53 and restores its transcriptional activity for tumor suppression.
The mechanism addresses a fundamental problem in cancer biology: most cancers inactivate p53, and restoring p53 function could reactivate the cell's own tumor suppression machinery.
Phase I clinical trial in adults with refractory solid tumors showed no dose-limiting toxicities at any dose level. The maximum tolerated dose was not reached. Stable disease was achieved in some patients. A pediatric Phase I study in CNS tumors also demonstrated favorable safety.
Phase I trials assess safety, not efficacy. No dose-limiting toxicities and disease stabilization are encouraging, but objective tumor responses (shrinkage) were not reported.
3 Human|157 Animal|40 Reviews
View all 40749 indexed studiesHow p28 (Azurin Peptide Fragment) Works
p28 is a 28-amino acid fragment of the bacterial protein azurin that preferentially enters cancer cells through caveolae-mediated endocytosis and stabilizes p53 by preventing HDM2-mediated proteasomal degradation.
Derived from a bacterial protein (azurin) that enters cancer cells and reactivates the main cancer-fighting protein (p53).
For a more detailed view of the biology, here is what researchers have observed at the molecular level.
p28 (amino acids 50-77 of Pseudomonas aeruginosa azurin) enters cells through caveolae-mediated endocytosis. Cancer cells have higher caveolar activity than normal cells, providing selectivity. Inside the cell, p28 binds the N-terminal domain of p53 (residues 80-276 region), preventing ubiquitination by HDM2 and COP1. This blocks proteasomal degradation and restores p53 transcriptional activity for cell cycle arrest (p21 activation), DNA repair (GADD45), and apoptosis (BAX, PUMA activation).
What is p28 (Azurin Peptide Fragment) being studied for?
Researchers are studying p28 (Azurin Peptide Fragment) across several health conditions. Each condition below is labeled with the strength of evidence that exists for that specific use, not for p28 (Azurin Peptide Fragment) overall. This means a compound can have human studies for one condition but only animal data for another.
Cancer Therapy
·Human TrialsPhase I trial in refractory solid tumors showed no dose-limiting toxicities and tumor stabilization in some patients. Pediatric Phase I in CNS tumors also showed favorable safety. The selective cancer cell entry mechanism is well-documented.
Limitations: Phase I assesses safety, not efficacy. Objective tumor responses were not reported. Phase II progression has not been publicly announced. Whether disease stabilization translates to survival benefit is unknown.
p53 Reactivation
·Animal Studiesp28 stabilizes wild-type p53 by preventing HDM2-mediated degradation. This has been demonstrated in multiple cancer cell lines and animal models.
Limitations: Applicable primarily to cancers that retain wild-type p53. Cancers with mutant p53 may not respond to stabilization alone. The proportion of cancers where this approach is relevant is a subset of all p53-altered tumors.
Safety and Regulatory Status
FDA Status: Not FDA-approved. Phase I clinical trial completed with favorable safety in both adult solid tumors and pediatric CNS tumors.
Availability: Investigational compound. Not available outside of clinical research.
Class context: No dose-limiting toxicities were observed in Phase I. Maximum tolerated dose was not reached, suggesting a favorable therapeutic window.
Favorable safety in Phase I. No dose-limiting toxicities at any dose level tested. The maximum tolerated dose was not reached in either the adult or pediatric trial. This suggests a wide therapeutic window.
Questions and Comparisons
Questions the evidence raises for a p28 (Azurin Peptide Fragment) discussion.
Comparison and Related Research
p28 is most often compared with other p53-targeting approaches and cancer-directed peptides.
Related compounds
Frequently Asked Questions
References
Each citation links to the original study on PubMed, the U.S. National Library of Medicine database.
- 1.Characterized the mechanism by which p28, a fragment of the bacterial protein azurin, preferentially enters cancer cells through caveolae-mediated endocytosis and stabilizes p53 to restore tumor suppressor function.Yamada T et al., 2009 in Mol Cancer Ther. View on PubMed
- 2.Phase I clinical trial in patients with refractory solid tumors showing that p28 was well tolerated across all dose levels tested. Maximum tolerated dose was not reached. Disease stabilization was observed in multiple tumor types.Warso MA et al., 2013 in J Clin Oncol. View on PubMed
- 3.Demonstrated that p28 inhibits tumor blood vessel formation through multiple signaling pathways (VEGFR-2, FAK, Akt), providing an anti-angiogenic mechanism that complements the p53 stabilization effect.Mehta RR et al., 2011 in Mol Cancer Ther. View on PubMed
- 4.Showed that p28 enhances the sensitivity of cancer cells to standard chemotherapy agents by activating p53 at a specific phase of the cell cycle, suggesting potential for combination therapy.Yamada T et al., 2014 in Sci Rep. View on PubMed
Medical Disclaimer
This content is for educational and informational purposes only and does not constitute medical advice. The information presented reflects published research as indexed by PSI and should not be used to make treatment decisions. Always consult a qualified healthcare provider before starting, stopping, or modifying any treatment.