Description
p38 is a member of the mitogen-
activated protein kinase (MAPK) superfamily of enzymes that play an important role in signal transduction. PD 169316 is a selective inhibitor of p38 MAPK.
1 It inhibits p38 MAPK with an IC
50 of 89 nM, whereas the IC
50s are >100-
fold higher for extracellular signal-
regulated kinase (ERK) and >1,000-
fold higher for protein kinase A (PKA) and PKCα.
1 PD 169316 inhibits apoptosis of neuronal and non-
neuronal cells deprived of specific trophic factors such as potassium or nerve growth factor.
2,3
Uses
PD 169316 is a highly selective, potent inhibitor of p38 MAP kinase. PD 169316 inhibits transforming growth factor β-induced Smad signaling in human ovarian cancer cells. PD 169316 acts as an an endogenous suppressor of apoptosis by mimicking CD9, a membrane tetraspanin. Studies show that PD 169316 reduces myocardial ischemia/reperfusion induced voltage-dependent anion channel(VDAC) phosphorylation
Definition
ChEBI: 4-[4-(4-fluorophenyl)-2-(4-nitrophenyl)-1H-imidazol-5-yl]pyridine is a member of imidazoles.
General Description
PD 169316 is a pyridinyl imidazole compound. It is a potential inhibitor of p38 mitogen-activated protein kinases. It also inhibits signalling transforming growth factor β (TGFβ), particularly in human ovarian cancer cells.
Biological Activity
Potent, cell permeable and selective inhibitor of p38 (SAPK2a).
Biochem/physiol Actions
Potent, cell-permeable and selective p38 MAP kinase inhibitor (IC50 = 89 nM).
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]
IC 50
a potent, selective and cell-permeable suppressor of p38 map kinase, with the ic50 value of 89 nm.
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.
