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PF-05175157

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Chemical Structure| 1301214-47-0 同义名 : -
CAS号 : 1301214-47-0
货号 : A724655
分子式 : C23H27N5O2
纯度 : 99%+
分子量 : 405.493
MDL号 : MFCD28502250
存储条件：

粉末 Keep in dark place,Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 30 mg/mL(73.98 mM)，配合低频超声，并水浴加热至45℃助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 Acetyl-CoA carboxylase (ACC) is a biotin carboxylase that catalyzes the ATP-dependent condensation of acetyl-CoA and carbonate to form malonyl-CoA. The malonyl-CoA is an essential and rate-limiting substrate for de novo lipogenesis (DNL), and it acts as an allosteric inhibitor of the enzyme carnitine-palmitoyl transferase I (CPT-1)[1]. PF-05175157 is broad spectrum acetyl-CoA carboxylase (ACC) inhibitor with IC50 values of 27.0, 33.0, 23.5 and 50.4 nM for ACC1 (human), ACC2 (human), ACC1 (rat), ACC2 (rat), respectively[2]. In the First-in-Human study, single ascending doses of PF-05175157 ranging from 10 to 800 mg were safe and well-tolerated. Fructose stimulated DNL was inhibited over this time course; peak fructose-stimulated fractional DNL was reduced by 63.6% (90% CI = 75.1–52.0%) relative to placebo treatment[2]. PF-05175157 shows antiviral activities against West Nile virus (WNV) dengue virus (DENV) and Zika virus (ZIKV) with EC50 values of 2.7 ± 1.3 µM, 1.0 ± 0.3 µM and < 1.2 µM, respectively[3]. Murine model of WNV infection were treated with PF-05175157 (20 mg/kg) or drug vehicle twice a day p.o.. When compared to control animals, mice treated with PF-05175157 exhibited a significant decrease of viral load in plasma at 3 and 4 days after infection, a significant reduction in the amount of viral RNA in the kidney and a tendency for a reduction in the amount of viral RNA in the lung[3].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.47mL

0.49mL

0.25mL

12.33mL

2.47mL

1.23mL

24.66mL

4.93mL

2.47mL
参考文献

[1]Saggerson D. Malonyl-CoA, a key signaling molecule in mammalian cells. Annu Rev Nutr. 2008;28:253-72. doi: 10.1146/annurev.nutr.28.061807.155434. PMID: 18598135.

[2]Griffith DA, Kung DW, Esler WP, Amor PA, Bagley SW, Beysen C, Carvajal-Gonzalez S, Doran SD, Limberakis C, Mathiowetz AM, McPherson K, Price DA, Ravussin E, Sonnenberg GE, Southers JA, Sweet LJ, Turner SM, Vajdos FF. 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):10512-26. doi: 10.1021/jm5016022. Epub 2014 Dec 11. PMID: 25423286; PMCID: PMC4281100.

[3]Jiménez de Oya N, Esler WP, Huard K, El-Kattan AF, Karamanlidis G, Blázquez AB, Ramos-Ibeas P, Escribano-Romero E, Louloudes-Lázaro A, Casas J, Sobrino F, Hoehn K, James DE, Gutiérrez-Adán A, Saiz JC, Martín-Acebes MA. Targeting host metabolism by inhibition of acetyl-Coenzyme A carboxylase reduces flavivirus infection in mouse models. Emerg Microbes Infect. 2019;8(1):624-636. doi: 10.1080/22221751.2019.1604084. PMID: 30999821; PMCID: PMC6493301.