Referencia número: HY-10721

PF-AKT400

(Synonyms: AKT protein kinase inhibitor)

Revisión del cliente

Based on 1 Customer Validation

PF-AKT400 is a broadly selective, potent, ATP-competitive Akt inhibitor, displays 900-fold greater selectivity for PKBα (IC₅₀=0.5 nM) than PKA (IC₅₀=450 nM).

Para uso exclusivo en investigación. No vendemos a pacientes.

Pureza: 98.0%
No. CAS: 1004990-28-6
Fòrmula: C₂₀H₂₂F₂N₆O
Peso molecular:400.43

Almacenamiento:

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

PF-AKT400 Chemical Structure

No. CAS: 1004990-28-6

Tamaño

Precio

Stock

Cantidad

Amount: USD 0.00

* Seleccione Cantidad antes de agregar artículos.

Top Publications Citing

Use of MCE Products

Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Actividad biológica
- Descripciòn
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
Chemical Information
Solvente y solubilidad
- In Vitro
- In Vivo
Protocolo
Pureza y Documentación
Referencias
Help & FAQs
Classifications
Bioz

Actividad biológica

Descripciòn

PF-AKT400 is a broadly selective, potent, ATP-competitive Akt inhibitor, displays 900-fold greater selectivity for PKBα (IC₅₀=0.5 nM) than PKA (IC₅₀=450 nM).

IC₅₀ & Target^[1]

PKBα

0.5 nM (IC₅₀)

PKA

450 nM (IC₅₀)

Ver todos los productos específicos de isoformas Akt :

Cellular Effect

Cell Line	Type	Value	Description	References
U-87MG ATCC	IC₅₀	0.31 μM Compound: 42	Inhibition of AKT1-mediated GSK3alpha phosphorylation in human U87 cells after 1 hr by ELISA Inhibition of AKT1-mediated GSK3alpha phosphorylation in human U87 cells after 1 hr by ELISA	[PMID: 20481595]

In Vitro

PF-AKT400 (Compound 42) provides significantly enhanced selectivity for Akt relative to earlier leads such as spiroindoline 2. Free IC₅₀ and EC₅₀ values are estimated for phospho-S6 reduction (110 nM) and Akt hyperphosphorylation (216 nM), respectively. These values corresponded well to the cellular IC₅₀ for PF-AKT400 in U87 cells measuring p-GSK-3α (310 nM)^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

PF-AKT400 is subsequently evaluated for modulation of Akt in tumors and in multiple in vivo mouse models of antitumor efficacy. It is active in a PC3 prostate carcinoma xenograft experiment, with 75% TGI observed at 100 mg/kg b.i.d. dosing for 10 days. In a colorectal carcinoma (Colo205) xenograft study, PF-AKT400 produces 60% TGI at 150 mg/kg b.i.d. after 10 days. Most intriguingly, in combination with Rapamycin (10 mg/kg, ip), 75 mg/kg b.i.d. (10 days) of PF-AKT400 results in 98% TGI in an additional PC3 prostate carcinoma xenograft study compared to 56% TGI and 66% TGI with PF-AKT400 and Rapamycin as single agents. To define the in vivo potency of PF-AKT400 (Compound 42) in the PC3 xenograft model, oral administration of 25, 75, and 100 mg/kg PF-AKT400 is performed with blood and tumor sampling over time. Immunoblot analysis of detergent-soluble extracts derived from PC3 tumors shows a significant reduction of S6 phosphorylation, and hyperphosphorylation of Akt upon treatment at doses that produced significant tumor growth inhibition. Plasma drug concentrations peak rapidly after oral administration of doses between 25-100 mg/kg (T_max=0.5 h). Peak PD responses of phospho-S6 and phospho-Akt are observed at approximately 2-4h and 1h post-administration of PF-AKT400, respectively. The time-course of PD marker response is well described by a PK/PD model at doses that ranged from no efficacy (25 mg/kg) to maximal efficacy (100 mg/kg)^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Chemical Information

No. CAS 1004990-28-6
Appearance Solid
Peso molecular 400.43
Fòrmula C₂₀H₂₂F₂N₆O
Color White to off-white
SMILES

N[C@@](CC1)(CNC(C2=CC=C(F)C=C2F)=O)CN1C3=C4C(NC=C4CC)=NC=N3
Synonyms

AKT protein kinase inhibitor
Envío

Room temperature in continental US; may vary elsewhere.

Almacenamiento

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

Solvente y solubilidad

In Vitro:

DMSO : ≥ 100 mg/mL (249.73 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

2.4973 mL

12.4866 mL

24.9732 mL

5 mM

0.4995 mL

2.4973 mL

4.9946 mL

10 mM

0.2497 mL

1.2487 mL

2.4973 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.

Calculadora de molaridad

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

Mass Mass

Concentration Concentration

Volume Volume

Molecular Weight Molecular Weight

Calculadora de dilución

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

Concentration _(start) Concentration _(start)

Volume _(start) Volume _(start)

Concentration _(final) Concentration _(final)

Volume _(final) Volume _(final)

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: ≥ 2.5 mg/mL (6.24 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.

Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)

Solubility: ≥ 2.5 mg/mL (6.24 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.

Protocol 3

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

Solubility: ≥ 2.5 mg/mL (6.24 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 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 (25.0 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

Protocolo

Kinase Assay^[2]

A fluorescence polarization IMAP type assay is used. An amount of 15 μL of diluted PF-AKT400 (Compound 42) in DMSO is mixed with 60 μL of reaction buffer (10 mM Tris-HCl, pH 7.5, 10 mM MgCl₂, 0.1 mM EGTA, 0.01% Triton-X100, 1 mM DTT). Then 5 μL of the compound/buffer mixture, 10 μL of a solution containing 4 μM ATP and 40 nM fluorescent-labeled Crosstide (Tamara-labeled GRPRTSSFAEG peptide), and 5 μL of Akt1 protein (lacking the pleckstrin homology (PH) domain, containing an Asp at position 473, and prephosphorylated at Thr 308) in reaction buffer are combined. After a 90 min incubation, IMAP beads are added and plates are read (lamp filter, 544 nm; emission filter, 615 nm). The same procedure can be applied to full length Akt1 to provide similar results. All IC₅₀ values are the geometric mean of at least n=2 determinations^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration^[2]

Mice^[2]
Studies to describe the PK/PD relationship for PF-AKT400 are performed in male SCID/Beige mice bearing subcutaneous PC3 prostate carcinoma xenografts. Once tumors reach about ~300mm³ in size, PF-AKT400 is formulated in 0.5% methylcellulose vehicle and administered orally to 3 mice per dose group. Plasma and tumors are harvested over time, tumor lysates prepared, and the levels of phospho S6 reduction and phospho Akt induction are evaluated by immunoblot.

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Pureza y Documentación

Select Batch:

Pureza: 99.98%

Assay: 99.98%

ee.: 99.98%

Ficha de datos (284 KB)
SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 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)
Instrucciones de manejo (2659 KB)

Referencias

[1]. Chen SF, et al. Binding selectivity studies of PKBα using molecular dynamics simulation and free energy calculations. J Mol Model. 2013 Nov;19(11):5097-5112. [Content Brief]

[2]. Freeman-Cook KD, et al. Design of selective, ATP-competitive inhibitors of Akt. J Med Chem. 2010 Jun 24;53(12):4615-4622. [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	2.4973 mL	12.4866 mL	24.9732 mL	62.4329 mL
	5 mM	0.4995 mL	2.4973 mL	4.9946 mL	12.4866 mL
	10 mM	0.2497 mL	1.2487 mL	2.4973 mL	6.2433 mL
	15 mM	0.1665 mL	0.8324 mL	1.6649 mL	4.1622 mL
	20 mM	0.1249 mL	0.6243 mL	1.2487 mL	3.1216 mL
	25 mM	0.0999 mL	0.4995 mL	0.9989 mL	2.4973 mL
	30 mM	0.0832 mL	0.4162 mL	0.8324 mL	2.0811 mL
	40 mM	0.0624 mL	0.3122 mL	0.6243 mL	1.5608 mL
	50 mM	0.0499 mL	0.2497 mL	0.4995 mL	1.2487 mL
	60 mM	0.0416 mL	0.2081 mL	0.4162 mL	1.0405 mL
	80 mM	0.0312 mL	0.1561 mL	0.3122 mL	0.7804 mL
	100 mM	0.0250 mL	0.1249 mL	0.2497 mL	0.6243 mL

Keywords

Nombre del producto:
Referencia número:
Cantidad:
MCE Japan Authorized Agent:

Nombre del producto:
No. CAS:
Species:
Pureza:
Cantidad:

PF-AKT400

Kinase Inhibitor Library

PI3K/Akt/mTOR Compound Library

Stem Cell Signaling Compound Library

Anti-Cancer Compound Library

Autophagy Compound Library

Anti-Aging Compound Library

Differentiation Inducing Compound Library

Oxygen Sensing Compound Library

Glycolysis Compound Library

Cytoskeleton Compound Library

Glutamine Metabolism Compound Library

Anti-Breast Cancer Compound Library

Anti-Lung Cancer Compound Library

Anti-Pancreatic Cancer Compound Library

Anti-Blood Cancer Compound Library

Anti-Cancer Metabolism Compound Library

Anti-Obesity Compound Library

Angiogenesis-Related Compound Library

Glucose Metabolism Compound Library

Targeted Diversity Library

Anti-Liver Cancer Compound Library

Anti-Colorectal Cancer Compound Library

Anti-Prostate Cancer Compound Library

Anti-Pulmonary Fibrosis Compound Library

Cancer Stem Cells Compound Library

Pain-Related Compound Library

Highly Selective Inhibitors Library

Serine/Threonine Kinase Inhibitor Library

Anti-Hematopathy Compound Library

Anti-Ovarian Cancer Compound Library

Multi-Target Compound Library

Bioactive Compound Library Max

MCE Bioactive Compound Library

Bioactive Compound Library

Anti-Gastric Cancer Compound Library

Anti-Fibrosis Compound Library

Protein Kinase Compound Library

Non-Alcoholic Fatty Liver Disease (NAFLD) Compound Library

Cell Proliferation Compound Library

High-Throughput Bioactive Compound Library

Posttranslational Modification Library

Lactylation Compound Library

Ver todos los productos específicos de isoformas Akt

Actividad biológica

Chemical Information

Solvente y solubilidad

Protocolo

Pureza y Documentación

Referencias

Help & FAQs

Complete Stock Solution Preparation Table

PF-AKT400 Related Classifications

HY-10721 Related Classifications