(S)-PHA533533
Based on 1 Customer Validation
(S)-PHA533533 is a CDK2 and CDK5 inhibitor with blood-brain barrier permeability, with IC50 values of 37 nM and 55 nM, respectively. (S)-PHA533533 effectively restores UBE3A expression by downregulating UBE3A-ATS and relieving the epigenetic silencing of paternal UBE3A in mature neurons. (S)-PHA533533 can be used for the research of Angelman syndrome.
Para uso exclusivo en investigación. No vendemos a pacientes.
- Pureza: 98.27%
- No. CAS: 437982-89-3
- Fòrmula: C19H22N4O2
- Peso molecular:338.40
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Almacenamiento:
4°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Actividad biológica
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Chemical Information
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Solvente y solubilidad
- Pureza y Documentación
- Referencias
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Help & FAQs
Actividad biológica
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| A2780 | IC50 |
0.8 μM
Compound: 1, PHA-533533
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Antiproliferative activity against human A2780 cells
Antiproliferative activity against human A2780 cells
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[PMID: 16616492] |
| HCT-116 | IC50 |
1354 nM
Compound: 13 (table 2)
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Inhibitory concentration towards HCT 116 human colon cancer cell line
Inhibitory concentration towards HCT 116 human colon cancer cell line
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[PMID: 15828833] |
| HT-29 | IC50 |
639 nM
Compound: 13 (table 2)
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Inhibitory concentration towards human colon cancer HT-29 cell line
Inhibitory concentration towards human colon cancer HT-29 cell line
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[PMID: 15828833] |
(S)-PHA533533 (1 μM; 72 h) potently activates paternal Ube3a expression in primary cortical neurons from Ube3am+/pYFP mice[1].
(S)-PHA533533 (72 h) activates paternal Ube3a expression in primary cortical neurons from Ube3am+/pYFP mice, with an EC50 of 0.54 μM, an EMAX of 80.02% paternal UBE3A-YFP-positive neurons, and a CC50 of 2.98 μM[1].
(S)-PHA533533 (1 μM; 72 h) activates paternal Ube3a expression in primary cortical neurons derived from Ube3am+/pYFP mice, and this process is independent of the inhibition of CDK2, CDK5 and TOP1[1].
(S)-PHA533533 (72 h) downregulates UBE3A-ATS and relieves the silencing of paternal UBE3A in forebrain cortical neurons derived from ASdel1-0ΔI-P human induced pluripotent stem cells, with an EC50 of 0.59 μM for UBE3A induction and an IC50 of 0.42 μM for UBE3A-ATS downregulation[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| Species | Dose | Route | CL | Cmax | AUC |
|---|---|---|---|---|---|
| Mice[1] | 10 mg/kg | p.o. | 5.8 mL/min/kg | 21 μM | 96 μM·h |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6J (Ube3am-/p+ Angelman syndrome model, postnatal day 11)[1]
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Dosage:2 mg/kg
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Administration:i.p.; single injection
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Result:Significantly increased Ube3a mRNA levels in all examined brain regions (olfactory bulb, cortex and hippocampus, subcortical tissues, cerebellum) compared to saline-treated control AS mice.
Reached Ube3a mRNA levels measured in saline-treated wild-type mice in the olfactory bulb.
Widespread reinstated UBE3A protein throughout the brain, with increased UBE3A signal detected in all NeuN-positive mature neurons across multiple brain regions.
Chemical Information
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No. CAS 437982-89-3
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Appearance Solid
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Peso molecular 338.40
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Fòrmula C19H22N4O2
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Color White to off-white
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SMILES
C[C@H](C(NC1=NNC(C2CC2)=C1)=O)C3=CC=C(N4CCCC4=O)C=C3
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
4°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
Solvente y solubilidad
DMSO : 100 mg/mL (295.51 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (7.39 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (7.39 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL. * In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Pureza y Documentación
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Ficha de datos (273 KB)
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SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
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Instrucciones de manejo (2659 KB)
Referencias
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.9551 mL | 14.7754 mL | 29.5508 mL | 73.8771 mL |
| 5 mM | 0.5910 mL | 2.9551 mL | 5.9102 mL | 14.7754 mL | |
| 10 mM | 0.2955 mL | 1.4775 mL | 2.9551 mL | 7.3877 mL | |
| 15 mM | 0.1970 mL | 0.9850 mL | 1.9701 mL | 4.9251 mL | |
| 20 mM | 0.1478 mL | 0.7388 mL | 1.4775 mL | 3.6939 mL | |
| 25 mM | 0.1182 mL | 0.5910 mL | 1.1820 mL | 2.9551 mL | |
| 30 mM | 0.0985 mL | 0.4925 mL | 0.9850 mL | 2.4626 mL | |
| 40 mM | 0.0739 mL | 0.3694 mL | 0.7388 mL | 1.8469 mL | |
| 50 mM | 0.0591 mL | 0.2955 mL | 0.5910 mL | 1.4775 mL | |
| 60 mM | 0.0493 mL | 0.2463 mL | 0.4925 mL | 1.2313 mL | |
| 80 mM | 0.0369 mL | 0.1847 mL | 0.3694 mL | 0.9235 mL | |
| 100 mM | 0.0296 mL | 0.1478 mL | 0.2955 mL | 0.7388 mL |
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