PF-05175157

PF-05175157 is broad spectrum acetyl-CoA carboxylase (ACC) inhibitor with IC50s of 27.0, 33.0, 23.5 and 50.4 nM for ACC1 (human), ACC2 (human), ACC1 (rat), ACC2 (rat), respectively.

Product information

CAS Number: 1301214-47-0

Molecular Weight: 405.49

Formula: C23H27N5O2

Chemical Name: 1'-(2-methyl-1H-1,3-benzodiazole-6-carbonyl)-1-(propan-2-yl)-1,4,6,7-tetrahydrospiro[indazole-5,4'-piperidin]-7-one

Smiles: CC1NC2=CC(=CC=C2N=1)C(=O)N1CCC2(CC(=O)C3=C(C2)C=NN3C(C)C)CC1

InChiKey: BDXXSFOJPYSYOC-UHFFFAOYSA-N

InChi: InChI=1S/C23H27N5O2/c1-14(2)28-21-17(13-24-28)11-23(12-20(21)29)6-8-27(9-7-23)22(30)16-4-5-18-19(10-16)26-15(3)25-18/h4-5,10,13-14H,6-9,11-12H2,1-3H3,(H,25,26)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 30 mg/mL (73.98 mM; Need ultrasonic and warming).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

PF-05175157 is broad spectrum acetyl-CoA carboxylase (ACC) inhibitor with IC50s of 27.0±2.7, 33.0±4.1, 23.5±1.1 and 50.4±2.6 nM for ACC1 (human), ACC2 (human), ACC1 (rat) and ACC2 (rat), respectively. 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).

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.

Products are for research use only. Not for human use.