PD 169316

PD 169316 is a potent, cell-permeable and selective p38 MAP kinase inhibitor, with IC₅₀ of 89 nM. PD169316 selectively inhibits the kinase activity of the phosphorylated p38 without hindering upstream kinases to phosphorylate p38. PD169316 shows antiviral activity against Enterovirus71. PD169316 shows antiviral activity against Enterovirus71. IC50 & Target: IC50: 89 nM (p38 MAPK)^[5] In Vitro: PD169316 (10 μM) inhibits TGFβ and Activin A, but not BMP4 signaling in CaOV3 cells. PD169316 (0.2-20 μM) inhibits TGFβ-induced Smad2 nuclear translocation, Smad7 mRNA induction, and reporter gene activity in CaOV3 cells^[1]. PD169316 (10 μM) shows a significantly increased rate of proliferation in Nestin knockdown cells, and can rescue the effect of Nestin knockdown on cell viability in the absence of EGF^[2]. PD169316 significantly inhibits p38 MAP kinase activity with no significant change in ERK activity in PC12 cells. PD169316 (10 μM) blocks apoptosis induced by trophic factor withdrawal in differentiated PC12 cells^[3].PD169316 (10 μM, 30 min) selectively inhibits the kinase activity of the phosphorylated p38 without hindering upstream kinases to phosphorylate p38. Increased phospho p-38 levels in the presence of PD169316 are most likely due to blockade of negative feedback loop of dephosphorylation of p38 MAPK by MAPK phosphatases^[4]. In Vivo: PD169316 (1 mg/kg, intramuscular injection every day for 14 consecutive days) shows antiviral activity in a suckling mouse model^[5].