950912-80-8
基本信息
CK1Ε抑制劑(PF-670462)
4-[1-環(huán)己基-4-(4-氟苯基)-1H-咪唑-5-基]-2-嘧啶胺鹽酸鹽
PF 67046
PF 670462
PF-670462 HCL
PF-670462 2HCl
PF 670462, >=98%
PF670462/ PF-670462
PF670462 dihydrochloride
PF-670462 (hydrochloride)
Casein Kinase I Inhibitor II, PF-670462
物理化學(xué)性質(zhì)
應(yīng)用領(lǐng)域
常見問題列表
Target | Value |
CK1δ
(Cell-free assay) | 13 nM |
CK1ε
(Cell-free assay) | 90 nM |
PF-670462 is a potent and selective inhibitor of CKIε and CKIδ, with IC 50 s of 7.7 nM and 14 nM, respectively. PF-670462 shows less than 30-fold selevtivity for EGFR and SAPK2A/p38, with IC 50 s of 150 nM and 190 nM, respectively. PF-670462 also causes a redistribution of the GFP signal to the cytoplasm in a concentration-dependent manner, with an EC 50 of 290 ± 39 nM in CKIε-transfected COS7 cells. PF-670462 is a potent inhibitor of Wnt/β-catenin signaling, with an IC 50 of ~17?nM. PF-670462 (1?μM) is a weak inhibitor of proliferation, and only modestly suppresses the growth of HEK293 and HT1080 cells. PF-670462 (100 nM) strongly inhibits CK1ε and CK1δ, consistent with its effect on Wnt/β-catenin signaling.
PF-670462 (50 mg/kg, s.c.) produces robust phase delays, and the activity remains persistent, with no discernible correction in the absence of exogenous zeitgebers in rats. PF-670462 (25, 50, and 100 mg/kg, s.c.) induces dose-dependent phase shift. PF-670462 (50 mg/kg; s.c.) significantly phase delays the rhythmic transcription of Bmal1, Per1, Per2 and Nr1d1 in both liver and pancreas by 4.5 ± 1.3 h and 4.5 ± 1.2 h, respectively, 1 day after administration. In the suprachiasmatic nucleus (SCN), the rhythm of Nr1d1 and Dbp mRNA expression is also delayed by 4.2 and 4 h, respectively.