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| Targets |
p53 amyloid formation[1].
ReACp53 targets amyloid aggregates of mutant p53 protein. p53 mutations are ubiquitous in high-grade serous ovarian carcinomas (HGSOC) and often lead to protein misfolding and aggregation into amyloid-like structures. ReACp53 binds to these aggregates, preventing further aggregation and restoring the normal folding and function of p53. It re-localizes p53 to the nucleus in an active conformation as a transcriptional factor. |
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| ln Vitro |
ReACp53 enters primary cancer cells HGSOC and changes mutant p53 from a punctate state to a soluble form that resembles WT p53. ReACp53 also causes p53 degradation, cell cycle arrest, and death of cancer cells. When cultivated as organoids, ReACp53 selectively affects the viability and proliferation of cancer cells expressing mutant p53 but not wild type[1].
In vitro, ReACp53 inhibits p53 amyloid formation and rescues p53 function in cancer cell lines and in organoids derived from HGSOC patients. It re-localizes p53 to the nucleus in an active conformation. The peptide induces mitochondrial cell death and reduces DNA synthesis of mutant p53-carrying PCa cells. It targets amyloid aggregates of mutant p53 and restores its transcriptional activity. |
| ln Vivo |
ReACp53 can inhibit tumor growth and reduce tumor size; only mutant p53-bearing tumors in the ReACp53-treated mice cohorts weigh 80–90% less than the control cohort. ReACp53-treated OVCAR3 xenografts show a marked decrease in Ki67 positive cells, which is suggestive of a lower proliferative index. In the minimal residual disease model, comparable outcomes are noted. According to the paradigm, p21 and MDM2 transcription is significantly increased in OVCAR3 xenografts but not in MCF7 xenografts when ReACp53 is administered. Upon ReACp53 injection in vivo, a markedly increased population is also observed in the G0/G1 phase, indicating proliferative arrest[1].
In vivo, ReACp53 inhibits xenograft tumor growth in mouse models. It has shown therapeutic potential in targeting mutant p53 protein in castration-resistant prostate cancer (CRPC). The peptide restores p53 nuclear function as a transcriptional factor, induces mitochondrial cell death, and reduces DNA synthesis. It has also been studied in models of high-grade serous ovarian carcinoma. |
| Enzyme Assay |
A cell-free binding assay for ReACp53 can be performed using thioflavin T (ThT) fluorescence to monitor p53 aggregation. Purified mutant p53 protein (e.g., p53-R248Q) is incubated with varying concentrations of ReACp53 (0.1-10 uM) in aggregation buffer at 37degC. ThT fluorescence (ex/em = 440/485 nm) is measured every 15 min for 24-48 h. The reduction in ThT fluorescence compared to the control indicates inhibition of amyloid fibril formation.
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| Cell Assay |
Mutant p53-expressing cancer cells (e.g., OVCAR3, which carries the R248Q p53 mutation) are seeded in 6-well plates. Cells are treated with ReACp53 (5-20 uM) for 24-48 h. The cell-penetrating peptide is added directly to the culture medium. After treatment, cells are harvested. p53 localization is analyzed by immunofluorescence staining with an anti-p53 antibody and DAPI nuclear counterstain. p53 transcriptional activity is measured by qPCR for p53 target genes (e.g., p21, PUMA, MDM2). Apoptosis is assessed by Annexin V/PI staining and flow cytometry. Cell viability is measured by MTT assay.
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| Animal Protocol |
ReACp53 can be studied in mouse xenograft models of cancer. Female NOD/SCID mice (6-8 weeks, n=8-10 per group) are implanted subcutaneously with OVCAR3 (HGSOC) or PC3 (prostate cancer) cells. When tumors reach 100-150 mm3, mice are randomized and treated intraperitoneally with ReACp53 (10-20 mg/kg) dissolved in PBS or 5% DMSO/PBS, once daily for 14-21 days. Tumor volume is measured every 2-3 days. At the end of the study, tumors are excised and analyzed for p53 localization (immunohistochemistry), p53 target gene expression (qPCR), and apoptosis (TUNEL).
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| ADME/Pharmacokinetics |
ReACp53 has a molecular weight of 2617.13 and the molecular formula C108H206N52O24. The peptide should be stored as a lyophilized powder at -20degC for up to 2-3 years. In solution (e.g., in PBS or water), it is stable for 1 month at -20degC or for 6 months at -80degC. Specific PK parameters have not been reported. As a 17-residue peptide, its plasma half-life is expected to be short (minutes to hours).
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| Toxicity/Toxicokinetics |
No detailed toxicity data for ReACp53 are available. In animal studies, the compound was well-tolerated at doses up to 20 mg/kg i.p. for up to 3 weeks, with no overt signs of systemic toxicity. As a peptide that targets mutant p53, the primary safety concern is potential effects on normal cells with wild-type p53. However, no significant toxicity has been reported. Standard safety precautions for peptide handling should be followed.
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| References | |
| Additional Infomation |
ReACp53 is a research-grade peptide and is not approved for clinical use. It is a cell-penetrating peptide that targets p53 amyloid aggregates and restores p53 function in cancer cells. It has shown promising anti-tumor effects in preclinical models of ovarian cancer and prostate cancer. This product is for research use only and not for human therapeutic applications.
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| Molecular Formula |
C108H206N52O24
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| Molecular Weight |
2617.13
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| Appearance |
White to off-white solid powder
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO :~100 mg/mL (~38.21 mM)
H2O :~25 mg/mL (~9.55 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (0.96 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (0.96 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (0.96 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 50 mg/mL (19.10 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.3821 mL | 1.9105 mL | 3.8210 mL | |
| 5 mM | 0.0764 mL | 0.3821 mL | 0.7642 mL | |
| 10 mM | 0.0382 mL | 0.1910 mL | 0.3821 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
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