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PF-06409577

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Chemical Structure| 1467057-23-3 同义名 : -
CAS号 : 1467057-23-3
货号 : A421471
分子式 : C19H16ClNO3
纯度 : 99%+
分子量 : 341.788
MDL号 : MFCD29917835
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(307.21 mM)，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 In eukaryotic cells AMP-activated protein kinase (AMPK) plays a major role in regulating cellular energy balance. AMPK responds to changes in intracellular adenine nucleotide levels, being activated by an increase in AMP/ADP relative to ATP. Activation of AMPK increases the rate of catabolic (ATP-generating) pathways and decreases the rate of anabolic (ATP-utilising) pathways[1]. PF-06409577 is a potent and selective allosteric activator of AMPK α1β1γ1 isoform with an EC50 of 7 nM[2]. In broad panel screening against other receptors, channels, PDEs and kinases, PF-06409577 exhibits minimal off-target pharmacology. PF-06409577 demonstrates moderate plasma clearance in rats, dogs, and monkeys, and is well distributed with steady state distribution volume. Following oral administration of crystalline PF-06409577 in 0.5% methylcellulose suspension, PF-06409577 is rapidly absorbed in rats, dogs, and monkeys. The corresponding oral bioavailability values in rats, dogs, and monkeys, are 15%, 100%, and 59%, respectively. Oral administration of PF-06409577 (10, 30, and 100 mg/kg QD) results in dose-dependent reductions in proteinuria in the obese ZSF1 animals, with greater than 2-fold reduction in 24-hour urinary albumin loss compared to vehicle control after 60 days of treatment[2].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.93mL

0.59mL

0.29mL

14.63mL

2.93mL

1.46mL

29.26mL

5.85mL

2.93mL
参考文献

[1]Carling D. AMPK signalling in health and disease. Curr Opin Cell Biol. 2017 Apr;45:31-37. doi: 10.1016/j.ceb.2017.01.005. Epub 2017 Feb 21. PMID: 28232179.

[2]Cameron KO, Kung DW, Kalgutkar AS, Kurumbail RG, Miller R, Salatto CT, Ward J, Withka JM, Bhattacharya SK, Boehm M, Borzilleri KA, Brown JA, Calabrese M, Caspers NL, Cokorinos E, Conn EL, Dowling MS, Edmonds DJ, Eng H, Fernando DP, Frisbie R, Hepworth D, Landro J, Mao Y, Rajamohan F, Reyes AR, Rose CR, Ryder T, Shavnya A, Smith AC, Tu M, Wolford AC, Xiao J. Discovery and Preclinical Characterization of 6-Chloro-5-[4-(1-hydroxycyclobutyl)phenyl]-1H-indole-3-carboxylic Acid (PF-06409577), a Direct Activator of Adenosine Monophosphate-activated Protein Kinase (AMPK), for the Potential Treatment of Diabetic Nephropathy. J Med Chem. 2016 Sep 8;59(17):8068-81. doi: 10.1021/acs.jmedchem.6b00866. Epub 2016 Aug 20. PMID: 27490827.