PF-5274857
Based on 1 Customer Validation
PF-5274857 is a potent, selective, orally active and brain-penetrant antagonist of Smo, with an IC50 of 5.8 nM and Ki of 4.6 nM. PF-5274857 has potential for research of tumor types including brain tumors and brain metastasis driven by an activated Hh pathway.
For research use only. We do not sell to patients.
- Purity: 99.31%
- CAS No.: 1373615-35-0
- Formula: C20H25ClN4O3S
- Molecular Weight:436.96
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Purity & Documentation
- References
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Help & FAQs
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Biological Activity
IC50: 5.8 nM (Smo); Ki: 4.6 nM (Smo)[1]
PF-5274857 completely inhibits Shh-induced Hh pathway activity with an IC50 of 2.7±1.4 nM measured by the transcriptional activity of Smo downstream gene Gli1 in MEF cells[1].
PF-5274857 shows less than 20% inhibition against a broad panel of protein kinases at 1 μM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
PF-5274857 (10 mg/kg; i.h.) in the plasma is able to cross the blood-brain barrier in rats within 4 hours postdose[1].
PF-5274857 (10-100 mg/kg; p.o. once daily for 4 days) is able to target Smo in the brain leading to the downregulation of Hh pathway activity in the brain tumor[1].
PF-5274857 (30 mg/kg; p.o. once daily for 34 days) increases the survival rates of primary Ptch+/? p53?/? medulloblastoma mice[1].
PF-5274857 (5-30 mg/kg; p.o.) exhibits the apparent volume of distribution of 5.6±0.5 L/kg and the half-life (T1/2) of 1.7±0.1 hours[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Severe combined immunodeficient (SCID)-beige mice (6-8 weeks old) are genetically engineered[1]
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Dosage:0, 1, 5, 10, 30 mg/kg
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Administration:P.o. once daily for 6 days
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Result:Showed robust antitumor activity with an in vivo IC50 of 8.9±2.6 nM.
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Animal Model:Severe combined immunodeficient (SCID)-beige mice (6-8 weeks old)[1]
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Dosage:0, 5, 10, 30 mg/kg (Pharmacokinetic Analysis)
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Administration:A single p.o.
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Result:The apparent volume of distribution of 5.6±0.5 L/kg; the half-life (T1/2) of 1.7±0.1 hours.
Chemical Information
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CAS No. 1373615-35-0
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Appearance Solid
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Molecular Weight 436.96
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Formula C20H25ClN4O3S
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Color Light yellow to yellow
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SMILES
O=C(N1CCN(C2=NC=C(Cl)C(C3=NC=C(C)C=C3C)=C2)CC1)CCS(=O)(C)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Solvent & Solubility
DMSO : 125 mg/mL (286.07 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
H2O : < 0.1 mg/mL (insoluble)
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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
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: ≥ 2.08 mg/mL (4.76 mM); Clear solution
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 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: ≥ 2.08 mg/mL (4.76 mM); Clear solution
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 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.
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.
Purity & Documentation
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Data Sheet (274 KB)
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SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Portuguese - PT (393 KB)
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Handling Instructions (2659 KB)
References
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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.2885 mL | 11.4427 mL | 22.8854 mL | 57.2135 mL |
| 5 mM | 0.4577 mL | 2.2885 mL | 4.5771 mL | 11.4427 mL | |
| 10 mM | 0.2289 mL | 1.1443 mL | 2.2885 mL | 5.7213 mL | |
| 15 mM | 0.1526 mL | 0.7628 mL | 1.5257 mL | 3.8142 mL | |
| 20 mM | 0.1144 mL | 0.5721 mL | 1.1443 mL | 2.8607 mL | |
| 25 mM | 0.0915 mL | 0.4577 mL | 0.9154 mL | 2.2885 mL | |
| 30 mM | 0.0763 mL | 0.3814 mL | 0.7628 mL | 1.9071 mL | |
| 40 mM | 0.0572 mL | 0.2861 mL | 0.5721 mL | 1.4303 mL | |
| 50 mM | 0.0458 mL | 0.2289 mL | 0.4577 mL | 1.1443 mL | |
| 60 mM | 0.0381 mL | 0.1907 mL | 0.3814 mL | 0.9536 mL | |
| 80 mM | 0.0286 mL | 0.1430 mL | 0.2861 mL | 0.7152 mL | |
| 100 mM | 0.0229 mL | 0.1144 mL | 0.2289 mL | 0.5721 mL |
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