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| 5mg |
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| 10mg |
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| 50mg |
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| Targets |
PhiKan 083 targets the p53 mutant Y220C. It binds to the surface cavity of this mutant, stabilizing the protein and increasing its functional half-life. The binding affinity is characterized by a Kd value of 167 µM. This stabilization is a strategy to reactivate p53's tumor-suppressive functions in cancers harboring this specific mutation.
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| ln Vitro |
PhiKan 083, a derivative of carbazole, has a Kd of 167 μM[1] and a relative binding affinity (Kd) of 150 μM for p53Y220C in Ln229 cells[3]. It binds to surface cavities and stabilizes Y220C (p53 mutant). Its thermal denaturation rate is slowed down by PhiKan 083 [2]. Engineered Ln229 cell variations' cell viability is decreased by PhiKan 083 (125 μM, 48 hours) [3]. In Ln229 cells, combining PhiKan 083 (100 μM) with NSC 123127 (1 μM) increases the pro-apoptotic activity of all variants (p53wt, p53Y220C, p53G245S, and p53R282W) [3].
In vitro, PhiKan 083 has been shown to reduce cell viability and enhance pro-apoptotic activity in Ln229 cell lines engineered to express various p53 mutants, including p53wt, p53Y220C, p53G245S, and p53R282W. It demonstrates a relative affinity (Kd) of 150 µM in Ln229 cells. When combined with NSC 123127 (1 µM), it potentiates pro-apoptotic effects. |
| ln Vivo |
In vivo studies for PhiKan 083 are limited to preclinical cancer models. As a research compound, it has not advanced to clinical trials. However, its mechanism of stabilizing mutant p53 suggests that in animal models of cancer, it could potentially suppress tumor growth and enhance the efficacy of other chemotherapeutic agents. Comprehensive in vivo efficacy data for this specific compound are not available.
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| Enzyme Assay |
The in vitro binding assay for PhiKan 083 involves techniques like surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC) to measure its interaction with the p53 Y220C mutant protein. The purified protein is immobilized, and varying concentrations of the compound are flowed over the surface to determine the binding affinity (Kd) and kinetics.
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| Cell Assay |
Cell Viability Assay [1]
Cell Types: Ln229, Ln229-p53-wt, Ln229-p53-Y220C, Ln229-p53-G245S, Ln229-p53-R282W Cell Tested Concentrations: 125 μM Incubation Duration: 48 hrs (hours) Experimental Results: Caused ∼70 ± The Ln229 cell variant had a 5% reduction in cell viability. In vitro cell culture studies are the primary method for evaluating PhiKan 083's activity. Ln229 glioblastoma cells, engineered to express different p53 mutants, are treated with the compound. Cell viability is assessed using standard assays like MTT or CellTiter-Glo. Apoptosis is measured by flow cytometry using Annexin V/propidium iodide staining. The expression of p53 target genes is analyzed by Western blotting or qPCR. |
| Animal Protocol |
In vivo animal experiments are not standard for this early-stage research compound. However, potential in vivo models would involve xenograft studies in immunodeficient mice, where human cancer cells harboring the p53 Y220C mutation are implanted. PhiKan 083 would be administered via intraperitoneal injection, and tumor growth would be monitored to assess its in vivo efficacy as a single agent or in combination with chemotherapy.
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| ADME/Pharmacokinetics |
PhiKan 083 has a molecular weight of 238.33 g/mol and is a solid compound with a purity of ≥95%. It is soluble in DMSO and ethanol. For in vivo studies, a formulation containing 10% DMSO, 40% PEG300, 5% Tween 80, and 45% saline is recommended. It is typically stored as a powder at -20°C, with stock solutions stable for up to one year at -80°C.
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| Toxicity/Toxicokinetics |
Toxicological data for PhiKan 083 are limited to in vitro cytotoxicity assessments. As a research compound targeting p53, it is not intended for human use, and its safety profile is not well characterized. Standard precautions for handling chemical research reagents should be followed, including the use of personal protective equipment.
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| References |
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| Additional Infomation |
PhiKan 083 is a research compound used for studying the p53 pathway. It serves as a valuable tool for exploring therapeutic strategies related to p53 mutations. By stabilizing the p53 mutant Y220C, it contributes to a better understanding of mutant p53 function and the development of targeted therapies for cancers associated with this specific mutation.
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| Molecular Formula |
C16H18N2.HCL
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|---|---|
| Molecular Weight |
274.78846
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| Exact Mass |
238.146
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| CAS # |
880813-36-5
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| Related CAS # |
PhiKan 083 hydrochloride;1050480-30-2
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| PubChem CID |
4722579
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| Appearance |
Colorless to light yellow solid powder
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| LogP |
4.726
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
1
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
18
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| Complexity |
278
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
LBPNOEAFWYTTEB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H18N2/c1-3-18-15-7-5-4-6-13(15)14-10-12(11-17-2)8-9-16(14)18/h4-10,17H,3,11H2,1-2H3
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| Chemical Name |
1-(9-ethylcarbazol-3-yl)-N-methylmethanamine
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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 |
| 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 (~419.59 mM)
Ethanol : ~100 mg/mL (~419.59 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (10.49 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. Solubility in Formulation 2: ≥ 2.17 mg/mL (9.11 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 21.7 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. View More
Solubility in Formulation 3: 2.17 mg/mL (9.11 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.6391 mL | 18.1957 mL | 36.3914 mL | |
| 5 mM | 0.7278 mL | 3.6391 mL | 7.2783 mL | |
| 10 mM | 0.3639 mL | 1.8196 mL | 3.6391 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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