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PF-670462 2HCl

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Chemical Structure| 950912-80-8 同义名 : PF-670462;PF-670462 dihydrochloride;PF-670462 (hydrochloride)
CAS号 : 950912-80-8
货号 : A124173
分子式 : C19H22Cl2FN5
纯度 : 99%+
分子量 : 410.316
MDL号 : MFCD12828759
存储条件：

粉末 Inert atmosphere,Room Temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 30 mg/mL(73.11 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

H2O: 100 mg/mL(243.71 mM)，配合低频超声助溶
动物实验配方：
生物活性
靶点

  • CK1

    CK1δ, IC50:13 nM

    CK1ε, IC50:90 nM
描述 CK1 kinases regulate diverse processes including Wnt signaling, membrane trafficking, the actin cytoskeleton, the DNA damage response, and circadian rhythms. Importantly, aberrant CK1δ and CK1ε activity is implicated in human pathologies, including neurodegenerative diseases, sleep disorders and cancer. PF-670462 is an effective and selective CK1ε and CK1δ inhibitor with IC50s of 90 nM and 13 nM, respectively[3]. A549 cells were treated with transforming growth factor-beta (TGF-β) (100 pM) for 48 h with PF670462 added 30 min prior to TGF-β. PF670462 concentration-dependently inhibited TGF-β-induced loss of E-cadherin expression, reaching a maximum effect at 3-10 μM PF670462. PF670462 (30 mg/kg/day, i.p.) attenuated bleomycin-induced accumulation of hydroxyproline and the number of infiltrating immune cells measured in the BAL fluid. In a separate study in female mice, aerosolised PF670462 (0.3-3.0 mg/ml, 15 min/once daily) corresponding to estimated deposited doses of ∼1-10 μg/day from day 8-20, also reduced hydroxyproline content, BALF cell influx, and fibrogenic gene expression at day 21[4].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.44mL

0.49mL

0.24mL

12.19mL

2.44mL

1.22mL

24.37mL

4.87mL

2.44mL
参考文献

[1]Walton KM, Fisher K, et al. Selective inhibition of casein kinase 1 epsilon minimally alters circadian clock period. J Pharmacol Exp Ther. 2009 Aug;330(2):430-9.

[2]Badura L, Swanson T, et al. An inhibitor of casein kinase I epsilon induces phase delays in circadian rhythms under free-running and entrained conditions. J Pharmacol Exp Ther. 2007 Aug;322(2):730-8.

[3]Bibian M, Rahaim RJ, Choi JY, Noguchi Y, Schürer S, Chen W, Nakanishi S, Licht K, Rosenberg LH, Li L, Feng Y, Cameron MD, Duckett DR, Cleveland JL, Roush WR. Development of highly selective casein kinase 1δ/1ε (CK1δ/ε) inhibitors with potent antiproliferative properties. Bioorg Med Chem Lett. 2013 Aug 1;23(15):4374-80. doi: 10.1016/j.bmcl.2013.05.075. Epub 2013 May 31. PMID: 23787102; PMCID: PMC3783656.

[4]Keenan CR, Langenbach SY, Jativa F, Harris T, Li M, Chen Q, Xia Y, Gao B, Schuliga MJ, Jaffar J, Prodanovic D, Tu Y, Berhan A, Lee PVS, Westall GP, Stewart AG. Casein Kinase 1δ/ε Inhibitor, PF670462 Attenuates the Fibrogenic Effects of Transforming Growth Factor-β in Pulmonary Fibrosis. Front Pharmacol. 2018 Jul 10;9:738. doi: 10.3389/fphar.2018.00738. PMID: 30042678; PMCID: PMC6048361.