生物活性

• 描述The TGF-β pathway regulates a wide variety of cellular processes in many different cell types and biological contexts. There are three identified TGF receptor ligands, TGF-β1, 2, and 3. Activated TGF-β ligands can interact with TGF-β type II receptors (TβRII), then recruit and phosphorylate the TGF-β type I receptors (also called as TβRI or ALK5). In turn, activated TβRI phosphorylates SMAD2 and SMAD3 at C-terminal serine residues. Following that, phosphorylated SMAD and SMAD3 assemble into heterodimeric and trimeric complexes with SMAD4. Then the trimeric complex translocate into the nucleus and regulate the expression of TGF-β target genes^[1]. SB-525334 is an ALK5 inhibitor with IC50 value of 14.3 nM, with modest potent to ALK4 with an IC50 value of 58.5 nM (measured by GST-ALKs kinase assay). Addition of 1 μM SB-525334 reduced TGF-β1-induced Smad2 and Smad3 nuclear localization back to the control levels in RPTE cells^[2]. SB-525334 on concentration of 0.5 - 2 μM can inhibit p-SMAD2 in dose-dependent manner in ELT-3 cells^[3]. SB525334, 30 mg/kg, given twice daily by oral gavage for 2 weeks can attenuate f bleomycin-induced lung fibrosis in mice^[4].

• 动物研究
  剂量	Rat[2] (p.o): min = 1 mg/kg, max = 10 mg/kg
  给药途径	p.o.
  动物药代数据	Animal Rats[2] Dose 10 mg/kg Administration p.o. T1/2 115 min CL 1 ml/min/100 g F 0.87