产品描述

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（IC50 & Targe）

CK1δ [1]

(Cell-free assay)

13 nM

CK1ε [1]

(Cell-free assay)

90 nM

体外研究

PF-670462 is a 14 nM inhibitor of CK1δ in vitro and also potently inhibits p38 and EGFR[1]. In vitro, PF670462 prevents TGF-β-induced epithelial-mesenchymal transition[2].

体内研究

PF670462 administered systemically or locally by inhalation prevents both acute and chronic bleomycin-induced pulmonary fibrosis in mice[2].

细胞实验

Cell lines: A549 cells

Concentrations: 0.3-10 μM

Incubation Time: 48 h

Method:A549 cells are left to adhere overnight. Cells are then serum-starved for 16 h prior to pre-incubation with PF670462 (0.3-10 μM) for 30 min then TGF-β (100 pM) for 48 h. Cells are fixed in 10% neutral buffered formalin for 15 min and non-specific binding sites are blocked by incubation with 5% normal goat serum/0.3% Triton X-100 in PBS for 1 h. E-Cadherin expression is detected by immunofluorescence staining.

(Only for Reference)

动物实验

Animal Models: Six- to eight-week old 20–25 g C57Bl/6 mice

Formulation: initially dissolved in 100% DMSO and prepared for injection by 1:10 dilution in Arachis oil

Dosages: 30 mg/kg/day

Administration: IP

(Only for Reference)

参考文献

[1] Mathieu Bibian, et al. Bioorg Med Chem Lett. 2013, 23(15): 4374–4380.

[2] Keenan CR, et al. Front Pharmacol. 2018, 9:738.