Azurin-p28
Also known as: AZU‑p28, Azurin‑derived peptide, Azurin‑derived peptide p28, Azurin‑p28, NSC745104, p28, p28-azurin
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Summary
Azurin‑p28 (p28) is a 28‑amino‑acid peptide fragment derived from the bacterial redox protein azurin. It is being investigated as an investigational anticancer peptide that preferentially penetrates solid‑tumor cells and, in preclinical models, inhibits tumor growth by stabilising p53 and disrupting endothelial signalling. Research to date is limited to in‑vitro cell work, animal xenograft studies, and pharmacokinetic/toxicology profiling.
Mechanism of Action
After selective entry into cancer cells, p28 binds both wild‑type and mutant p53, blocking the E3 ligase Cop1 and preventing ubiquitin‑mediated proteasomal degradation of p53. The resulting p53 accumulation triggers G2/M cell‑cycle arrest and apoptosis. p28 also enters nascent endothelial cells, where it reduces phosphorylation of focal‑adhesion kinase (FAK) and Akt, impairing cell motility and angiogenic processes. These dual actions underlie its reported antitumour activity.
What the Research Shows
Preclinical studies show that p28 penetrates tumour cells in a dose‑dependent manner, suppresses growth of p53‑positive solid‑tumour xenografts, and enhances apoptosis via mitochondrial caspase pathways. A chimeric protein combining p28 with the antimicrobial peptide NRC displayed greater cytotoxicity against breast‑cancer lines than p28 alone. In colon‑cancer models, p28 alone or with the tumor‑penetrating peptide iRGD and 5‑fluorouracil increased p53 and pro‑apoptotic BAX while lowering anti‑apoptotic BCL2, augmenting tumour regression. Pharmacokinetic profiling in mice revealed rapid clearance (t½ ≈0.23 h) and broad tissue distribution, with a non‑immunogenic profile and no overt toxicity at doses up to 120 mg kg⁻¹ intravenously in females. Toxicity in male mice manifested as reversible reductions in heart and thymus weight, while non‑human primates tolerated up to 120 mg kg⁻¹ without adverse effects. No human clinical trial data are reported.
Reported Benefits
The peptide’s selective entry into tumour cells and ability to stabilise both wild‑type and mutant p53 suggest potential efficacy across a range of solid tumours, including those resistant to conventional chemotherapy. Animal data indicate tumour growth inhibition at doses that were well tolerated, and the lack of detectable immunogenicity supports repeated administration. Combination strategies with tumor‑penetrating peptides or standard chemotherapeutics have shown additive pro‑apoptotic effects in preclinical colon‑cancer models.
Limitations of the Evidence
All efficacy evidence is confined to cell‑culture and animal studies; no human safety or efficacy data have been published. Activity appears dependent on p53 status, limiting applicability to p53‑positive tumours. Toxicity signals in male mice (reversible organ‑weight changes) and the peptide’s short plasma half‑life raise formulation and dosing challenges. The preclinical nature of the data means regulatory approval has not been achieved, and translational relevance remains uncertain.
Safety Considerations
Preclinical toxicology reports describe p28 as non‑immunogenic and non‑toxic in female mice and non‑human primates at doses up to 120 mg kg⁻¹ intravenously. Male mice exhibited reversible reductions in heart and thymus weight at similar exposures, but no lethal toxicity. The peptide is rapidly cleared (clearance ≈1.7 L kg⁻¹ h⁻¹) and has a short half‑life (~0.23 h), suggesting limited systemic exposure. No adverse events were observed in the studied animal species at the reported no‑observed‑adverse‑effect levels.
How It Is Administered
Azurin‑p28 has been administered intravenously and subcutaneously in preclinical studies; intraperitoneal dosing was used in mouse efficacy experiments. Formulations described involve peptide solutions suitable for injection, but specific excipients or delivery systems are not detailed in the cited literature.
Routes of Administration
Goals & Uses
- Cancer therapyOncologyModerate
- Solid tumor treatmentOncologyModerate
- Glioblastoma adjunct therapyOncologyLow
- Pediatric CNS tumor treatmentOncologyModerate
- Anti-angiogenesisOncology / VascularLow
- Solid tumor therapy (breast, melanoma, liver)OncologyModerate
- Glioblastoma multiforme treatmentOncologyModerate
- p53 pathway restorationMolecular TargetModerate
Contraindications
- Known hypersensitivity to azurin-p28 or bacterial-derived peptidesAllergy/immunologyHigh
- PregnancyPopulationHighPotential fetal risk or insufficient safety data
- Known hypersensitivity to azurin or related bacterial proteinsAllergyModerate
- Tumors with mutant/null p53MolecularModerate
- Known hypersensitivity to azurin‑derived peptidesAllergyModerate
Adverse Effects
- HeadacheNeurologicUncommonPain in the head or upper neck
- Elevated liver enzymes (transaminitis)HepaticUncommon
- Infusion‑related reactionsGeneralCommon
- NauseaGastrointestinalCommonFeeling of sickness or urge to vomit
- FatigueGeneralUncommonLow energy or tiredness
- Infusion-related reactionsHypersensitivityUncommon
- Infusion‑related reactionGeneralCommon
Drug Interactions
- MDM2 inhibitors (e.g., nutlin-3, RG7112)Low
- Cytotoxic chemotherapy (general)Low
- Concurrent chemotherapy agentsModerate
- CYP450 substratesLow
Population Constraints
- Pediatric patientsAgeRelative
- Pregnant or breastfeeding womenReproductiveRelative
- Severe hepatic impairmentOrgan ImpairmentRelative
- Pediatric patients (<3 years)PediatricRelative
Regulatory Status
- European UnionUnknownNo EU marketing authorization as of 2026
- United StatesInvestigationalInvestigational New Drug (IND) status; orphan drug designation for glioblastoma
- United KingdomUnknownNo MHRA approval or designation confirmed
Orphan drug designation granted in the United States for certain solid tumors; no approved indication as of 2026.
Evidence & Sources
- Journal ArticleLowSoleimani M, Mirmohammmad Sadeghi H, Jahanian-Najafabadi A2019-01-01T00:00:00.000000Z
- Journal ArticleModerateYaghoubi A, et al.2020-01-01T00:00:00.000000Z
- Journal ArticleLowJia L, et al.2011-01-01T00:00:00.000000Z
- Journal ArticleModerateKarpiński TM, Adamczak A2018-01-01T00:00:00.000000Z
- Journal ArticleLowGorman GS, et al.2010-01-01T00:00:00.000000Z
- Journal ArticleLowYaghoubi A, et al.2023-01-01T00:00:00.000000Z
Frequently Asked Questions
What type of cancers might benefit from p28 treatment?
Preclinical work indicates activity against solid tumours that retain functional p53, such as breast and colon cancers. The peptide’s mechanism relies on stabilising p53, so tumours lacking p53 or with non‑responsive pathways may be less responsive.
Has p28 been tested in humans?
No human clinical trial data are presented in the available abstracts. All reported findings are from cell‑culture experiments, mouse xenograft models, and toxicology studies in rodents and non‑human primates.
Are there known side effects of p28?
Animal studies reported no immunogenicity or overt toxicity at doses up to 120 mg kg⁻¹ in females. Male mice showed reversible reductions in heart and thymus weight, and the peptide has a short plasma half‑life, indicating rapid clearance.
Can p28 be combined with existing chemotherapy?
In a colon‑cancer study, p28 combined with the tumor‑penetrating peptide iRGD and the chemotherapeutic 5‑fluorouracil enhanced p53 and pro‑apoptotic BAX expression while lowering BCL2, suggesting additive anti‑tumour effects in preclinical models.
How is p28 delivered in research settings?
Researchers have administered p28 by intravenous injection, subcutaneous injection, and intraperitoneal injection in animal models, typically as a sterile peptide solution suitable for injection.
What is Azurin-p28?
Azurin‑p28 (p28) is a 28‑amino‑acid peptide fragment derived from the bacterial redox protein azurin. It is being investigated as an investigational anticancer peptide that preferentially penetrates solid‑tumor cells and, in preclinical models, inhibits tumor growth by stabilising p53 and disrupting endothelial signalling. Research to date is limited to in‑vitro cell work, animal xenograft studies, and pharmacokinetic/toxicology profiling.
What is Azurin-p28 used for?
Azurin-p28 is educationally associated with: Cancer therapy, Solid tumor treatment, Glioblastoma adjunct therapy, Pediatric CNS tumor treatment, Anti-angiogenesis, Solid tumor therapy (breast, melanoma, liver), Glioblastoma multiforme treatment, p53 pathway restoration. Educational only — not medical advice.
How is Azurin-p28 administered?
Recorded routes of administration: Intravenous, Subcutaneous.
What are the potential side effects of Azurin-p28?
Reported adverse effects include: Headache, Elevated liver enzymes (transaminitis), Infusion‑related reactions, Nausea, Fatigue, Infusion-related reactions, Infusion‑related reaction. This list is not exhaustive — consult a qualified clinician.
Who should avoid Azurin-p28?
Recorded contraindications: Known hypersensitivity to azurin-p28 or bacterial-derived peptides, Pregnancy, Known hypersensitivity to azurin or related bacterial proteins, Tumors with mutant/null p53, Known hypersensitivity to azurin‑derived peptides. Consult a qualified clinician before use.