PF-05175157

製品コードS6672 バッチS667201

印刷

化学情報

Synonyms

N/A

Storage
(From the date of receipt)

3 years -20°C powder

化学式

C₂₃H₂₇N₅O₂

分子量

405.49

CAS No.

1301214-47-0

Solubility (25°C)*

体外

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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	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.
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]

プロトコル(参考用のみ)

細胞アッセイ	細胞株	rat hepatocytes
	濃度	--
	反応時間	5 h
	実験の流れ	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.
動物実験	動物モデル	Male SD rats
	投薬量	0.25mg/kg, 0.5mg/kg, 1mg/kg, 2mg/kg, 4mg/kg, 8mg/kg, 15mg/kg, 25mg/kg, 50mg/kg and 100 mg/kg
	投与方法	Oral

参考

[1] David A Griffith,et al.J Med Chem.2014;57 (24): 10512-10526.

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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

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

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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