Art. -Nr.: HY-18056

PF-915275

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PF-915275 is a potent, selective and orally active human 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) inhibitor with a K_i 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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Reinheit: 98.59%
CAS. Nr.: 857290-04-1
Formel: C₁₈H₁₄N₄O₂S
Molecular Weight:350.39

Speicherung:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year

PF-915275 Chemical Structure

CAS. Nr.: 857290-04-1

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Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
Chemical Information
Lösungsmittel & Löslichkeit
- In Vitro
- In Vivo
Reinheit & Dokumentation
Verweise
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

IC₅₀ & Target

Ki: 2.3 nM (11βHSD1); EC50: 15 nM (11βHSD1)^[1]

Cellular Effect

Cell Line	Type	Value	Description	References
3T3-L1	EC₅₀	23.55 μM Compound: PF-915275	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	[PMID: 31294974]
HEK293	EC₅₀	5 nM Compound: 2, PF-915275	Inhibition of 11beta-HSD1 in human HEK293 cells Inhibition of 11beta-HSD1 in human HEK293 cells	[PMID: 23489629]
HEK293	EC₅₀	5 nM Compound: 26, PF-915275	Inhibition of human 11beta-HSD1 in HEK293 cells Inhibition of human 11beta-HSD1 in HEK293 cells	[PMID: 19473839]
HEK293	IC₅₀	>500 μM Compound: PF-915275	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	[PMID: 31294974]
Hepatocyte	EC₅₀	100 nM Compound: 26, PF-915275	Inhibition of 11beta-HSD1 in monkey hepatocytes Inhibition of 11beta-HSD1 in monkey hepatocytes	[PMID: 19473839]
Hepatocyte	EC₅₀	120 nM Compound: 26, PF-915275	Inhibition of 11beta-HSD1 in dog hepatocytes Inhibition of 11beta-HSD1 in dog hepatocytes	[PMID: 19473839]
Hepatocyte	EC₅₀	14500 nM Compound: 26, PF-915275	Inhibition of 11beta-HSD1 in rat hepatocytes Inhibition of 11beta-HSD1 in rat hepatocytes	[PMID: 19473839]
Hepatocyte	EC₅₀	20 nM Compound: 26, PF-915275	Inhibition of 11beta-HSD1 in human hepatocytes Inhibition of 11beta-HSD1 in human hepatocytes	[PMID: 19473839]

In Vitro

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.

In Vivo

The inhibition of either cortisone or prednisone turnover with PF-915275 yields similar EC₅₀ values to that in human hepatocytes (EC₅₀ by PF-915275 is 18 and 13 nM using cortisone and prednisone substrates, respectively) in vivo 11βHSD1 activity^[1].
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.

Animal Model:

Adult male cynomolgus monkeys (2-5 kg)^[1]
Dosage:

0.1 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg
Administration:

Oral administration; for 8 hours
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

CAS. Nr. 857290-04-1
Appearance Solid
Molecular Weight 350.39
Formel C₁₈H₁₄N₄O₂S
Color White to pink
SMILES

N#CC1=CC=C(C2=CC=C(S(NC3=NC(N)=CC=C3)(=O)=O)C=C2)C=C1
Versand

Room temperature in continental US; may vary elsewhere.

Speicherung

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Lösungsmittel & Löslichkeit

In Vitro:

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.

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

2.8540 mL

14.2698 mL

28.5396 mL

5 mM

0.5708 mL

2.8540 mL

5.7079 mL

10 mM

0.2854 mL

1.4270 mL

2.8540 mL

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.

Molaritätsrechner

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

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.

Protocol 1

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.

Protocol 2

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.

Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil

Solubility: ≥ 0.83 mg/mL (2.37 mM); Clear solution

This protocol yields a clear solution of ≥ 0.83 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (8.3 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
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

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (274 KB)
SDS (254 KB)
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- Swedish - SV (254 KB)
- Italian - IT (254 KB)
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- Portuguese - PT (254 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

Verweise

[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]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

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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PF-915275

Metabolism/Protease Compound Library

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Orally Active Compound Library

Human Metabolite Library

Heterocyclic Compound Library

Metabolic Enzyme Compound Library

Highly Selective Inhibitors Library

Bioactive Compound Library Max

MCE Bioactive Compound Library

Clinical Compound Library Plus

Bioactive Compound Library

High-Throughput Bioactive Compound Library

Mass Spectrometry Human Metabolite Library

Biologische Aktivität

Chemical Information

Lösungsmittel & Löslichkeit

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

PF-915275

Metabolism/Protease Compound Library

Clinical Compound Library

Orally Active Compound Library

Human Metabolite Library

Heterocyclic Compound Library

Metabolic Enzyme Compound Library

Highly Selective Inhibitors Library

Bioactive Compound Library Max

MCE Bioactive Compound Library

Clinical Compound Library Plus

Bioactive Compound Library

High-Throughput Bioactive Compound Library

Mass Spectrometry Human Metabolite Library

Biologische Aktivität

Chemical Information

Lösungsmittel & Löslichkeit

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

PF-915275 Related Classifications

HY-18056 Related Classifications