Azurin-p28

Summary

Azurin-p28 is a cell-penetrating anticancer peptide derived from the cupredoxin azurin of Pseudomonas aeruginosa. It selectively enters cancer cells, stabilizes tumor suppressor p53, and has shown activity against a range of solid tumors including breast cancer and CNS malignancies. It has completed Phase I clinical trials in adults and has been evaluated in pediatric recurrent/refractory CNS tumors.

Mechanism of Action

Azurin-p28 is a 28-amino-acid fragment derived from the bacterial protein azurin (Pseudomonas aeruginosa). It penetrates cancer cells preferentially, binds to the central hydrophobic domain of p53, inhibits ubiquitination and proteasomal degradation of p53, and stabilizes wild-type p53 protein levels, leading to cell cycle arrest and apoptosis in tumor cells. It also inhibits STAT3 signaling and angiogenesis.

Routes of Administration

Goals & Uses

• 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
• Tumors with mutant/null p53MolecularModerate

Adverse Effects

• HeadacheNeurologicUncommonPain in the head or upper neck
• Elevated liver enzymes (transaminitis)HepaticUncommon
• NauseaGastrointestinalCommonFeeling of sickness or urge to vomit
• FatigueGeneralCommonLow energy or tiredness
• Infusion-related reactionsHypersensitivityUncommon

Drug Interactions

• MDM2 inhibitors (e.g., nutlin-3, RG7112)Low
• Cytotoxic chemotherapy (general)Low

Population Constraints

• Pregnant or breastfeeding womenReproductiveRelative
• Severe hepatic impairmentOrgan ImpairmentRelative
• Pediatric patients (<3 years)PediatricRelative

Regulatory Status

• European UnionUnknownNo EMA approval or designation confirmed
• United StatesInvestigationalFDA Orphan Drug Designation granted for GBM; multiple completed Phase I trials; no approved indication
• United KingdomUnknownNo MHRA approval or designation confirmed

Received FDA Orphan Drug Designation for glioblastoma multiforme. Investigated under IND. No FDA or EMA approval. Phase I trials completed; Phase II trials have been explored in CNS tumors.

Evidence & Sources

No sources recorded yet.