PF-915275
Based on 1 Customer Validation
PF-915275 is a potent, selective and orally active human 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) inhibitor with a Ki of 2.3 nM and an EC50 of 15 nM (in HEK293 cells). The dose-dependent effect of PF-915275 on conversion of cortisone to cortisol in primary human and monkey hepatocytes, with an EC50 of 20 and 100 nM, respectively.
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- Purity: 98.59%
- CAS No.: 857290-04-1
- 화학식: C18H14N4O2S
- 분자량:350.39
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보관:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
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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Biological Activity
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Chemical Information
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용액&용해도
- 순도&문서
- References
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Help & FAQs
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Metabolism/Protease Compound Library
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Biological Activity
Ki: 2.3 nM (11βHSD1); EC50: 15 nM (11βHSD1)[1]
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| 3T3-L1 | EC50 |
23.55 μM
Compound: PF-915275
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Cytotoxicity against mouse 3T3L1 cells measured after 72 hrs by celltiter-glo luminescent cell viability assay
Cytotoxicity against mouse 3T3L1 cells measured after 72 hrs by celltiter-glo luminescent cell viability assay
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[PMID: 31294974] |
| HEK293 | EC50 |
5 nM
Compound: 2, PF-915275
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Inhibition of 11beta-HSD1 in human HEK293 cells
Inhibition of 11beta-HSD1 in human HEK293 cells
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[PMID: 23489629] |
| HEK293 | EC50 |
5 nM
Compound: 26, PF-915275
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Inhibition of human 11beta-HSD1 in HEK293 cells
Inhibition of human 11beta-HSD1 in HEK293 cells
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[PMID: 19473839] |
| HEK293 | IC50 |
>500 μM
Compound: PF-915275
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Inhibition of 11beta-HSD2 (unknown origin) expressed in HEK293 cells using cortisone as substrate measured after 2 hrs in presence of NAD+ by HTRF assay
Inhibition of 11beta-HSD2 (unknown origin) expressed in HEK293 cells using cortisone as substrate measured after 2 hrs in presence of NAD+ by HTRF assay
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[PMID: 31294974] |
| Hepatocyte | EC50 |
100 nM
Compound: 26, PF-915275
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Inhibition of 11beta-HSD1 in monkey hepatocytes
Inhibition of 11beta-HSD1 in monkey hepatocytes
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[PMID: 19473839] |
| Hepatocyte | EC50 |
120 nM
Compound: 26, PF-915275
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Inhibition of 11beta-HSD1 in dog hepatocytes
Inhibition of 11beta-HSD1 in dog hepatocytes
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[PMID: 19473839] |
| Hepatocyte | EC50 |
14500 nM
Compound: 26, PF-915275
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Inhibition of 11beta-HSD1 in rat hepatocytes
Inhibition of 11beta-HSD1 in rat hepatocytes
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[PMID: 19473839] |
| Hepatocyte | EC50 |
20 nM
Compound: 26, PF-915275
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Inhibition of 11beta-HSD1 in human hepatocytes
Inhibition of 11beta-HSD1 in human hepatocytes
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[PMID: 19473839] |
PF-915275 is a potent inhibitor of 11βHSD1 (in vitro HEK293, EC50 of 15 nM) in this human 11βHSD1 overexpressed cell line when coincubated in the presence of 300 nM enzyme substrate. Consistent with the species differences between human and rodent observed in biochemical assays, PF-915275 is a poor inhibitor of 11βHSD1 in rat FAO hepatoma cells, with an EC50 of 14,500 nM. PF-915275 demonstrates species-dependent potency for inhibiting cellular conversion of cortisone to cortisol in dog, monkey, and human in primary hepatocytes, with activity in human hepatocytes/monkey hepatocytes/dog hepatocytes. PF-915275 does not significantly inhibit 11βHSD2 (only 1.5% inhibition when tested at 10 μM). The dose-dependent effect of PF-915275 on conversion of cortisone to cortisol in primary human and monkey hepatocytes, with an EC50 of 20 and 100 nM, respectively[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
PF-915275 dose-dependently inhibits 11βHSD1-mediated conversion of prednisone to prednisolone. A maximum of 87% inhibition is observed, with the highest tested dose of 3 mg/kg[1].
The half-life of PF-915275 is 22 hours in monkey[1].
PF-915275 (0.1-3 mg/kg; oral administration; for 8 hours; male cynomolgus monkeys) treatment shows a trend in dose-dependent lowering of fed plasma insulin after 8 h of dosing in these monkeys. Plasma insulin levels are significantly lowered (by 54 and 60%, respectively) at 1 and 3 mg/kg PF-915275 treatment. Plasma glucose or lipid levels are not altered with treatment[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Adult male cynomolgus monkeys (2-5 kg)[1]
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Dosage:0.1 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg
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Administration:Oral administration; for 8 hours
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Result:There was a trend in dose-dependent lowering of fed plasma insulin after 8 h of dosing in these monkeys. Plasma insulin levels were significantly lowered (by 54 and 60%, respectively).
Chemical Information
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CAS No. 857290-04-1
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Appearance Solid
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분자량 350.39
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화학식 C18H14N4O2S
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Color White to pink
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SMILES
N#CC1=CC=C(C2=CC=C(S(NC3=NC(N)=CC=C3)(=O)=O)C=C2)C=C1
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
용액&용해도
DMSO : ≥ 31 mg/mL (88.47 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
* "≥" means soluble, but saturation unknown.
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: ≥ 0.83 mg/mL (2.37 mM); Clear solution
This protocol yields a clear solution of ≥ 0.83 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (8.3 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: ≥ 0.83 mg/mL (2.37 mM); Clear solution
This protocol yields a clear solution of ≥ 0.83 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (8.3 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.
순도&문서
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Data Sheet (274 KB)
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SDS (254 KB)
- English - EN (254 KB)
- Français - FR (254 KB)
- Deutsch - DE (254 KB)
- Norwegian - NO (254 KB)
- Español - ES (254 KB)
- Swedish - SV (254 KB)
- Italian - IT (254 KB)
- Korean - KR (254 KB)
- Portuguese - PT (254 KB)
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Handling Instructions (2659 KB)
References
[1]. Bhat BG, et al. Demonstration of proof of mechanism and pharmacokinetics and pharmacodynamic relationship with 4'-cyano-biphenyl-4-sulfonic acid (6-amino-pyridin-2-yl)-amide (PF-915275), an inhibitor of 11 -hydroxysteroid dehydrogenase type 1, in cynomolgus monkeys. J Pharmacol Exp Ther. 2008 Jan;324(1):299-305. [Content Brief]
[2]. Siu M, et al. N-(Pyridin-2-yl) arylsulfonamide inhibitors of 11beta-hydroxysteroid dehydrogenase type 1: Discovery of PF-915275. Bioorg Med Chem Lett. 2009 Jul 1;19(13):3493-7. [Content Brief]
[3]. Courtney R, et al. Modulation of 11beta-hydroxysteroid dehydrogenase (11betaHSD) activity biomarkers and pharmacokinetics of PF-00915275, a selective 11betaHSD1 inhibitor. J Clin Endocrinol Metab. 2008 Feb;93(2):550-6. [Content Brief]
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 | 2.8540 mL | 14.2698 mL | 28.5396 mL | 71.3491 mL |
| 5 mM | 0.5708 mL | 2.8540 mL | 5.7079 mL | 14.2698 mL | |
| 10 mM | 0.2854 mL | 1.4270 mL | 2.8540 mL | 7.1349 mL | |
| 15 mM | 0.1903 mL | 0.9513 mL | 1.9026 mL | 4.7566 mL | |
| 20 mM | 0.1427 mL | 0.7135 mL | 1.4270 mL | 3.5675 mL | |
| 25 mM | 0.1142 mL | 0.5708 mL | 1.1416 mL | 2.8540 mL | |
| 30 mM | 0.0951 mL | 0.4757 mL | 0.9513 mL | 2.3783 mL | |
| 40 mM | 0.0713 mL | 0.3567 mL | 0.7135 mL | 1.7837 mL | |
| 50 mM | 0.0571 mL | 0.2854 mL | 0.5708 mL | 1.4270 mL | |
| 60 mM | 0.0476 mL | 0.2378 mL | 0.4757 mL | 1.1892 mL | |
| 80 mM | 0.0357 mL | 0.1784 mL | 0.3567 mL | 0.8919 mL |
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