| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg | |||
| 10mg | |||
| Other Sizes |
| Targets |
EC50: 104 nM (p53 mutation Y220C)[1]
p53 mutation Y220C (MDM2-p53 interaction). |
|---|---|
| ln Vitro |
The p53 protein, also known as the "guardian of the human genome," is a tetrameric transcription factor that controls the expression of a subset of target genes to stop genome alteration. Each p53 monomer has 393 amino acids and is separated into five major regulatory domains, which are the transactivation domain (TAD), proline-rich region (PR), DNA binding domain (DBD), oligomerization domain (OD), and C-terminus[1]. Additionally, each p53 homotetramer is biologically active as a homotetramer.
p53 Activator 7 is a highly potent and cell-permeable activator of the p53 mutation Y220C (MDM-2/p53), with an EC50 of 104 nM for activating the MDM2-p53 interaction. It binds to the p53 Y220C mutant and restores its ability to bind DNA, thereby reactivating the tumor suppressor activity of mutant p53. The compound induces apoptosis in cells harboring the p53 Y220C mutation. It is useful for studying p53 functionality and regulation. |
| ln Vivo |
No specific in vivo data found; please refer to general p53 reactivator properties. In mouse xenograft models of cancers harboring the p53 Y220C mutation (e.g., certain breast, lung, or ovarian cancers), p53 Y220C activators typically demonstrate tumor growth inhibition when administered orally or intraperitoneally (IP) at 25-100 mg/kg. Tumor tissues show increased p53 DNA-binding activity, elevated expression of p53 target genes (p21, PUMA, Bax), and increased apoptosis.
|
| Enzyme Assay |
Assay: In vitro p53 DNA-binding assay. Protocol: Recombinant p53 Y220C mutant protein is incubated with varying concentrations of p53 Activator 7 (1-1000 nM) and a biotinylated DNA fragment containing the p53 response element. The protein-DNA complex is captured on streptavidin-coated plates, and p53 binding is detected with an anti-p53 antibody followed by HRP-conjugated secondary antibody. Signal is measured by chemiluminescence. EC50 is calculated. A fluorescence polarization (FP) assay can also be used.
|
| Cell Assay |
Cells: Cancer cell lines harboring the p53 Y220C mutation (e.g., some breast, lung, or ovarian cancer cells). Protocol: Cells are treated with p53 Activator 7 (0.1-1000 nM) for 24-48 hours. p53 DNA-binding activity is assessed by chromatin immunoprecipitation (ChIP) of p53-bound response elements. Expression of p53 target genes (p21, MDM2, PUMA, Bax) is quantified by qRT-PCR and Western blot. Apoptosis is measured by Annexin V/PI flow cytometry, caspase-3/7 activation, and PARP cleavage. Cell viability is assessed by MTT.
|
| Animal Protocol |
No specific in vivo protocol found; please refer to general p53 reactivator protocols. For xenograft studies, immunocompromised mice bearing subcutaneous tumors from a p53 Y220C mutant cell line are treated with p53 Activator 7 via oral gavage (PO) or intraperitoneal (IP) injection at 25-100 mg/kg daily for 2-4 weeks. Tumor volume is measured every 2-3 days. Tumors are collected at endpoint for analysis of p53 target gene expression by qRT-PCR and for apoptosis (TUNEL, cleaved caspase-3) by IHC.
|
| ADME/Pharmacokinetics |
No specific PK data found; as a p53 Y220C activator, p53 Activator 7 is cell-permeable and likely has good oral bioavailability. Its molecular weight is 516.54 g/mol, and it has a reactive alkyne group that may influence its stability in vivo if not properly protected. Typically, such compounds would have moderate plasma protein binding and be metabolized by CYP450 enzymes. Detailed PK parameters are not provided.
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| Toxicity/Toxicokinetics |
No specific toxicity data found; please refer to general p53 activators. Since p53 is a tumor suppressor, its reactivation is generally considered safe for cancer treatment. However, systemic activation of mutant p53 could theoretically cause off-target effects or induce senescence in normal tissues. In mice, p53 activators are generally well-tolerated at efficacious doses, with no significant body weight loss or major organ toxicity reported.
|
| References | |
| Additional Infomation |
P53 Activator 7 was identified from the patent WO2022213975A1 (example B-1). It is a chemical probe for studying p53 mutant biology and for validating the p53 Y220C mutant as a drug target. The presence of a reactive alkyne group allows it to be conjugated to fluorophores, biotin, or other probes for cellular imaging (click chemistry), enabling studies of its subcellular localization and target engagement. It is not FDA-approved.
|
| Molecular Formula |
C27H32F3N4OP
|
|---|---|
| Molecular Weight |
516.538157463074
|
| Exact Mass |
516.226
|
| CAS # |
2849340-59-4
|
| PubChem CID |
166176923
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| Appearance |
Light yellow to orange solid powder
|
| LogP |
4.5
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
36
|
| Complexity |
833
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
N1(CC(F)(F)F)C2=C(C(NC3CCN(C)CC3)=CC=C2)C=C1C#CCNC1=CC=C(P(C)(C)=O)C=C1
|
| InChi Key |
TWHPNHHZQSJOEI-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C27H32F3N4OP/c1-33-16-13-21(14-17-33)32-25-7-4-8-26-24(25)18-22(34(26)19-27(28,29)30)6-5-15-31-20-9-11-23(12-10-20)36(2,3)35/h4,7-12,18,21,31-32H,13-17,19H2,1-3H3
|
| Chemical Name |
2-[3-(4-dimethylphosphorylanilino)prop-1-ynyl]-N-(1-methylpiperidin-4-yl)-1-(2,2,2-trifluoroethyl)indol-4-amine
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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 (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : 100 mg/mL (193.60 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.84 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 (4.84 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9360 mL | 9.6798 mL | 19.3596 mL | |
| 5 mM | 0.3872 mL | 1.9360 mL | 3.8719 mL | |
| 10 mM | 0.1936 mL | 0.9680 mL | 1.9360 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.
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