PF-05175157

Catalog No.S6672 Batch:S667201

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Technical Data

Formula

C23H27N5O2

 

Molecular Weight 405.49 CAS No. 1301214-47-0
Solubility (25°C)* In vitro DMSO 30 mg/mL (73.98 mM)
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description PF-05175157 is a broad-spectrum effective ACC inhibitor with IC50 of 27.0 nM, 33.0 nM, 23.5 nM and 50.4 nM for human ACC1, human ACC2, rat ACC1, and rat ACC2, respectively.
Targets
rACC1 [1]
(Cell-free assay)
hACC1 [1]
(Cell-free assay)
hACC2 [1]
(Cell-free assay)
rACC2 [1]
(Cell-free assay)
23.5 nM 27.0 nM 33.0 nM 50.4 nM
In vitro

The in vitro metabolism of PF-05175157 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, suggesting it is a substrate for 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

In vivo, the plasma clearance of PF-05175157 is low following intravenous (iv) administration (1 mg/kg) to rats, dogs, and monkeys. Oral (po) administration (3 mg/kg) to rats and dogs showed bioavailability of 40% and 54%, respectively, consistent with the low microsomal clearance and good solubility at low pH. The bioavailability following a 50 mg/kg oral dose in rats was 106%, suggesting saturation of clearance. Formation of the direct product of ACC, malonyl-CoA, in the skeletal muscle and liver of lean Sprague Dawley 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. [1]

Protocol (from reference)

Cell Assay:

[1]

  • Cell lines

    rat hepatocytes

  • Concentrations

    --

  • Incubation Time

    5 h

  • Method

    On the day of the study, media was aspirated and cells are treated with fresh MCM media containing DMSO vehicle or varying concentrations of PF-05175157 as indicated. Compound was initially dissolved in DMSO and subsequently diluted 1:100 in MCM.After 5 h at 37 °C, incubation media is removed and the experiment is terminated by washing the cells with ice cold PBS.

Animal Study:

[1]

  • Animal Models

    Male SD rats

  • Dosages

    0.25mg/kg, 0.5mg/kg, 1mg/kg, 2mg/kg, 4mg/kg, 8mg/kg, 15mg/kg, 25mg/kg, 50mg/kg and 100 mg/kg

  • Administration

    Oral

Selleck's PF-05175157 has been cited by 1 publication

Imaging the metabolic reprograming of fatty acid synthesis pathway enables new diagnostic and therapeutic opportunity for breast cancer [ Cancer Cell Int, 2023, 23(1):83] PubMed: 37120513

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.