PD 169316

IC50: A potent, selective and cell-permeable suppressor of p38 MAP kinase, with the IC50 value of 89 nM.

PD169316, a specific p38 MAPK inhibitor, blocks signal transduction mediated by both TGF-β and Activin A, but not bone morphogenetic protein (BMP) 4. Suppression on TGF-β signaling in a dose-dependent manner may then reduce Smad2 and Smad3 phosphorylation, block nuclear translocation and increase the expression of TGF-β target gene. [1]

In vitro: It was reported that pretreatment of CaOV3 cells with 10 M PD169316 caused a significant decrease in Smad2 and Smad3 phosphorylation which was mediated by TGF-β. The inhibitory effect of PD 169316 was proved to act in a dose-dependent manner. Study also demonstrated that PD169316 at 5 M or higher dose directly suppressed TGF-β signaling activity. [1]

In vivo: Based on an amyloid β (Aβ) rat model of Alzheimer's disease, the effect of PD 169316 on apoptosis induced by amyloid beta was examined. It was demonstrated that caspase-3 and Bax/Bcl-2 ratio, two marks of apoptosis, were significantly decreased in the rats pre-treated with PD169316 intracerebroventricularly. This study suggested the potential neuroprotective role of PD 169316 against the neuronal toxicity induced by Aβ. [2]

Clinical trial: So far, no clinical trial has been conducted.

References:
[1]Fu YX, O’Connor LM, Shepherd TG and Nachtigal MW.  The p38 MAPK inhibitor, PD169316, inhibits transforming growth factor β-induced Smad signaling in human ovarian cancer cells. Biochem Bioph Res Co. 2003. 310: 3917.
[2]Ashabi G, Alamdary SZ, Ramin M and Khodagholi F.  Reduction of hippocampal apoptosis by intracerebroventricular administration of extracellular signal-regulated protein kinase and/or P38 inhibitors in amyloid beta rat model of Alzheimer’s disease: involvement of nuclear-related factor-2 and nuclear factor-κb. Basic Clin. Pharmacol. Toxicol. 2013 Aug. 112: 145–55.