4-[1-环己基-4-(4-氟苯基)-1H-咪唑-5-基]-2-嘧啶胺盐酸盐
中文名称:
4-[1-环己基-4-(4-氟苯基)-1H-咪唑-5-基]-2-嘧啶胺盐酸盐
中文同义词:
4-[1-环己基-4-(4-氟苯基)-1H-咪唑-5-基]-2-嘧啶胺盐酸盐;CK1Ε抑制剂(PF-670462);化合物PF670462
英文名称:
4-[1-Cyclohexyl-4-(4-fluorophenyl)-1H-imidazol-5-yl]-2-pyrimidinaminedihydrochloride
英文同义词:
PF670462/ PF-670462;4-[1-Cyclohexyl-4-(4-fluorophenyl)-1H-imidazol-5-yl]-2-pyrimidinamine hydrochloride;2-PyriMidinaMine, 4-[1-cyclohexyl-4-(4-fluorophenyl)-1H-iMidazol-5-yl]-, hydrochloride (1:2);PF 67046;4-[1-Cyclohexyl-4-(4-fluorophenyl)-1H-imidazol-5-yl]-2-pyrimidinamine hydrochloride PF670462;4-[3-Cyclohexyl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl]-pyrimidin-2-ylamine dihydrochloride;PF 670462, >=98%;PF 670462
CAS号:
950912-80-8
分子式:
C19H20FN5.2HCl
分子量:
410
EINECS号:
相关类别:
小分子抑制剂，天然产物;信号转导通路激酶抑制剂;抑制剂;小分子抑制剂;细胞生物学试剂;Inhibitors;Aromatics;Heterocycles;Intermediates Fine Chemicals;Pharmaceuticals;Protein Kinase Inhibitors and Activators
Mol文件:
950912-80-8.mol
储存条件
2-8°C
溶解度
H2O: soluble2mg/mL, clear (warmed)
形态
powder
颜色
white to beige
InChIKey
PSNKGVAXBSAHCH-UHFFFAOYSA-N
生物活性
PF-670462是有效的、选择性CK1ε和CK1δ抑制剂，IC50分别为90 nM和13 nM。
靶点
Target Value
CK1δ
(Cell-free assay) 13 nM
CK1ε
(Cell-free assay) 90 nM
Target
Value
CK1δ
(Cell-free assay)
13 nM
CK1ε
(Cell-free assay)
90 nM
体外研究
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.
体内研究
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.
用途
PF 670462 is a potent and selective casein kinase 1蔚 (CK1蔚) and CK1δ inhibitor. PF 670462 has been shown to inhibit PER protein nuclear translocation causing phase shifts in circadian rhythms. PF 6704 62 attenuates methamphetamine-stimulated locomotion in vivo.
WGK Germany
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