1. Others
  2. Others

PF-05175157 

Cat. No.: HY-12942
Handling Instructions

PF-05175157 (Compound 9) is a potent Acetyl-CoA carboxylase (ACC1) inhibitor with IC50s of 23.5±1.1 nM (rat) and 27.0±2.7 nM (human).

For research use only. We do not sell to patients.
PF-05175157 Chemical Structure

PF-05175157 Chemical Structure

CAS No. : 1301214-47-0

Size Price Stock Quantity
10 mM * 1 mL in DMSO $88 In-stock
5 mg $80 In-stock
10 mg $140 In-stock
50 mg   Get quote  
100 mg   Get quote  

* Please select Quantity before adding items.

Customer Review

  • Biological Activity

  • Protocol

  • Technical Information

  • References

Description

PF-05175157 (Compound 9) is a potent Acetyl-CoA carboxylase (ACC1) inhibitor with IC50s of 23.5±1.1 nM (rat) and 27.0±2.7 nM (human).

IC50 & Target

IC50: 23.5±1.1 nM (ACC1, rat), 27.0±2.7 nM (ACC1, human)[1]

In Vitro

The in vitro metabolism of PF-05175157 (Compound 9) is evaluated in microsomes from rat, dog, and human hepatocytes. PF-05175157 is not metabolized in rat, dog, or human microsomes. PF-05175157 is also stable in human hepatocyte incubations, but is minimally metabolized by recombinant human CYP3A4 and CYP3A5. PF-05175157 inhibits formation of malonyl-CoA in a concentration-dependent manner with a potency (EC50=30 nM) in rat hepatocytes consistent with its potency against rat ACC1 (24 nM)[1].

In Vivo

Oral administration (3 mg/kg) to rats and dogs show bioavailability of 40% and 54%, respectively, consistent with the low microsomal clearance and good solubility at low pH. Formation of the direct product of ACC, malonyl-CoA, in the skeletal muscle and liver of lean rats is assessed 1 h following an acute oral dose of PF-05175157, showing concentration-dependent reductions in both skeletal muscle and liver malonyl-CoA. At the nadir, quadriceps and liver malonyl-CoA levels are reduced by 76% and 89%, respectively. The EC50s for inhibition of quadriceps and liver malonyl-CoA are 870 and 540 nM, respectively, determined from unbind plasma concentrations of PF-05175157. Acute oral administration of PF-05175157 inhibits hepatic DNL in rats in an unbind plasma drug concentration-dependent manner. PF-05175157 inhibits up to 82% of the incorporation of [14C]acetate into [14C]lipids with an EC50 of 326 nM[1].

References
Preparing Stock Solutions
Concentration Volume (DMSO) Mass 1 mg 5 mg 10 mg
1 mM 2.4662 mL 12.3308 mL 24.6615 mL
5 mM 0.4932 mL 2.4662 mL 4.9323 mL
10 mM 0.2466 mL 1.2331 mL 2.4662 mL
Cell Assay
[1]

PF-05175157 (Compound 9) is initially dissolved in DMSO and subsequently diluted 1:100 in MCM. An aliquot of this solution is added to the fresh MCM in each well, further diluting the PF-05175157 by 1:10. This dilution progression ensures that all wells have a final DMSO concentration of 0.1%[1].

On the day of the study, media is aspirated and cells are treated with fresh MCM media containing DMSO vehicle or varying concentrations of PF-05175157 (Compound 9). After 5 h at 37 °C, incubation media is removed and the experiment is terminated by washing the cells with ice-cold PBS[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

Immediately prior to initiation of the study, the dosing solutions are prepared in dosing vehicle (0.5% methyl cellulose: 0.1% polysorbate 80), giving a final dosing volume of 5 mL/kg[1].

Male SD rats are weighed and randomized by body weight into treatment groups consisting of vehicle, 0.25, 0.5, 1, 2, 4, 8, 15, 25, 50, and 100 mg/kg of PF-05175157 (Compound 9). Animals are orally dosed 2 h into the light cycle with their respective treatments and fed ad libitum. One hour postdose, the animals are sacrificed via CO2 asphyxiation following by cervical dislocation. Blood for plasma exposure of PF-05175157 is collected via cardiac puncture, transferred to tubes with K2EDTA, centrifuged at 4 °C, and the plasma transferred to a 96-well microtiter plate and stored at -20 °C. Liver and quadriceps are rapidly removed, freeze-clamped in a clamp, and subsequently stored at -80 °C[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

405.49

Formula

C₂₃H₂₇N₅O₂

CAS No.

1301214-47-0

Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

DMSO: 30 mg/mL

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

Inquiry Online

Your information is safe with us. * Required Fields.

Product name

 

Salutation

Applicant name *

 

Email address *

Phone number

 

Organization name *

Country *

 

Requested quantity *

Remarks

Bulk Inquiry

Inquiry Information

Product Name:
PF-05175157
Cat. No.:
HY-12942
Quantity: