| Size | Price | Stock | Qty |
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| 5mg |
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| 25mg |
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| 100mg |
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Purity: ≥98%
PF-05175157 (PF05175157) is a novel, potent and selective broad spectrum inhibitor of acetyl-CoA carboxylase (ACC) with anti-diabetic and anticancer activity. It inhibits ACC with IC50s of 27.0, 33.0, 23.5 and 50.4 nM for ACC1 (human), ACC2 (human), ACC1 (rat), ACC2 (rat), respectively. Acetyl-CoA carboxylase (ACC) inhibitors offer significant potential for the treatment of type 2 diabetes mellitus (T2DM), hepatic steatosis, and cancer. However, the identification of tool compounds suitable to test the hypothesis in human trials has been challenging. ACC inihibitors inhibit de novo lipogenesis and increase β-oxidation of long-chain fatty acids with potential for treatment of type 2 diabetes, hepatic steatosis, and cancer.
| ln Vitro |
PF-05175157 is a broad-spectrum coenzyme A carboxylase (ACC) enzyme, with IC50 values for ACC1 (human), ACC2 (human), ACC1 (structure), and ACC2 (structure), respectively, being 27.0±2.7 and 33.0±4.1. 23.5±1.1 and 50.4±2.6 nM. In locus, dog, and human hepatocyte microsomes, the peripheral consequences of compound 9 (PF-05175157) were assessed. In mapping dog or human hepatocytes, PF-05175157 was not dependent on microsomes. When PF-05175157 is added in suspension, human hepatocytes exhibit negligible inhibition of malonite-CoA. Formation and efficacy (EC50=30 nM) matched the usage of supplemental ACC1 (24 nM) [1].
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| ln Vivo |
PF-05175157 (3 mg/kg; surface documentation) showed bioavailability of 40% and 54% in solution and in dogs, respectively, consistent with low microsomal clearance and good solubility at low pH. PF-05175157 evaluated the formation of propylene glycol-CoA, a direct product of ACC, in slimming molds and molds 1 hour after immediate mold casting, showing a decrease in the concentration of propylene glycol-CoA in molds and molds. At the nadir, quadriceps and spindle malonyl-CoA levels were lowered by 76% and 89%, respectively. The EC50s for inhibition of strand binding to quadriceps and spindle malonyl-CoA were 870 and 540 nM, respectively, as determined by unconcentrated PF-05175157. The acute wound formulation of PF-05175157 inhibits dye DNL in a non-binding drug concentration regulated way. An acute wound formulation of PF-05175157 including 82% [14C] saline with [14C] modulator exhibits an EC50 of 326 nM [1].
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| References |
[1]. David A, et al. Decreasing the Rate of Metabolic Ketone Reduction in the Discovery of a Clinical Acetyl-CoA Carboxylase Inhibitor for the Treatment of Diabetes. J Med Chem. 2014 Dec 26; 57(24): 10512–10526
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| Molecular Formula |
C23H27N5O2
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|---|---|
| Molecular Weight |
405.492784738541
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| CAS # |
1301214-47-0
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| SMILES |
O=C1CC2(CCN(C(C3=CC=C4N=C(C)NC4=C3)=O)CC2)CC5=C1N(C(C)C)N=C5
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| InChi Key |
BDXXSFOJPYSYOC-UHFFFAOYSA-N
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| InChi Code |
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)
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| Chemical Name |
1,4-Dihydro-1'-[(2-methyl-1H-benzimidazol-6-yl)carbonyl]-1-(1-methylethyl)-spiro[5H-indazole-5,4'-piperidin]-7(6H)-one
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| Synonyms |
PF05175157; PF-05175157; PF 05175157.
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~30 mg/mL (~73.98 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (2.47 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1 mg/mL (2.47 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 1 mg/mL (2.47 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 Plasma concentrations of1and its alcohol metabolite1min beagle dogs following oral administration of1at 10 mg/kg.J Med Chem.2014 Dec 26;57(24):10512-26. |
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 Co-crystal structure of1bound in the CT-domain binding domain of ACC. Compound1was oriented in the channel by hydrogen bonds between the ketone and NH-Gly-B1958 and between the amide carbonyl and NH-Glu-B2026.J Med Chem.2014 Dec 26;57(24):10512-26. |
 Plasma concentrations of9and its alcohol metabolite9min beagle dogs following oral administration of9at 3 mg/kg.J Med Chem.2014 Dec 26;57(24):10512-26. |
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