Home Metabolism Acetyl-CoA carboxylase inhibitor PF-05175157 For research use only.

PF-05175157

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.

PF-05175157 Chemical Structure

PF-05175157 Chemical Structure

CAS No. 1301214-47-0

Purity & Quality Control

Batch: S667201 DMSO]30 mg/mL]false]]]false]]]false Purity: 99.85%
99.85

PF-05175157 Related Products

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
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]
Cell Research 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.
In Vivo
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]
Animal Research 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
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02100527 Withdrawn
Acne Vulgaris
Pfizer
 April 2014 Phase 2
NCT02053116 Terminated
Type 2 Diabetes Mellitus
Pfizer
 March 2014 Phase 2
NCT02053103 Terminated
Type 2 Diabetes Mellitus
Pfizer
 March 2014 Phase 2
NCT01807377 Completed
Diabetes Mellitus Type 2
Pfizer
 April 2013 Phase 1
NCT01792635 Terminated
Diabetes Mellitus Type 2
Pfizer
 December 2012 Phase 2
NCT01537497 Completed
Diabetes Mellitus Type 2
Pfizer
 March 2012 Phase 1

Chemical Information & Solubility

Molecular Weight 405.49 Formula

C23H27N5O2

 
CAS No. 1301214-47-0 SDF --
Smiles CC1=NC2=C(N1)C=C(C=C2)C(=O)N3CCC4(CC3)CC5=C(C(=O)C4)N(N=C5)C(C)C
Storage (From the date of receipt) 3 years -20°C powder

In vitro
Batch:

DMSO : 30 mg/mL ( (73.98 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)


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In vivo
Batch:

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In vivo Formulation Calculator

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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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