PF-05175157

SKU: orb1226590

Description

PF-05175157 (PF-5175157) is a potennt Acetyl-CoA carboxylase (ACC) inhibitor with IC50 of 27 and 33 nM for hAAC1 and hACC2, respectively; shows concentration-dependent reductions in both skeletal muscle and liver malonyl-CoA with EC50 of 870 and 540 nM after 1 h following an acute oral dose in rats; demonstrates significant potential for the treatment of type 2 diabetes mellitus (T2DM).Diabetes Phase 2 Discontinued(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.

Key Properties

• CAS Number: 1301214-47-0
• MW: 405.49
• Purity: >98% (HPLC)
• Formula: C₂₃H₂₇N₅O₂
• SMILES: O=C1CC2(CCN(C(C3=CC=C4N=C(C)NC4=C3)=O)CC2)CC5=C1N(C(C)C)N=C5
• Target: ACC
• Solubility: DMSO : 30 mg/mL. 73.98 mM

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

PF05175157 | PF-5175157

Quick Database Links

Gene Symbol

ACC