PD 169316

• CAT Number: I001889
• CAS Number: 152121-53-4
• Molecular Formula: C₂₀H₁₃FN₄O₂
• Molecular Weight: 360.34
• Purity: ≥95%
• Synonyms: 4-[4-(4-fluorophenyl)-2-(4-nitrophenyl)-1H-imidazol-5-yl]pyridine
• Target: p38
• Solubility: DMSO 10 mg/mL; Water <1 mg/mL
• Storage: Store at -20C
• IC50: 89 nM
• InChI: InChI=1S/C20H13FN4O2/c21-16-5-1-13(2-6-16)18-19(14-9-11-22-12-10-14)24-20(23-18)15-3-7-17(8-4-15)25(26)27/h1-12H,(H,23,24)
• InChIKey: BGIYKDUASORTBB-UHFFFAOYSA-N
• SMILES: C1=CC(=CC=C1C2=NC(=C(N2)C3=CC=NC=C3)C4=CC=C(C=C4)F)[N+](=O)[O-]

PD 169316 is a potent, cell-permeable and selective p38 MAP kinase inhibitor (IC50 = 89 nM).IC50 Value: 89 nMTarget：p38 MAPKin vitro: PD169316, a p38 MAPK inhibitor, abrogates signaling initiated by both TGFbeta and Activin A, but not bone morphogenetic protein (BMP) 4. Inhibition of TGFbeta signaling is dose dependent and results in reduced Smad2 and Smad3 phosphorylation, nuclear translocation, and up-regulation of the TGFbeta target gene Smad7. Reduced TGFbeta signaling is not due to abrogation of p38 MAPK activity, since blocking p38 MAPK activity with a dominant negative form of p38 MAPK has no effect on TGFbeta/Smad signaling. PD169316 at 5 μM or higher can block TGFβ signaling activity and thus caution must be used when attributing cellular activities exclusively to p38 MAPK signaling when these inhibitors are used experimentally [1]. PD169316 significantly attenuated apoptosis in potassium-deprived cells in a dose dependent manner [2]. PD169316 rescued the inhibitory effect of sphingosine on the formation of inositol phosphates by PGF(2alpha) or NaF in osteoblast-like MC3T3-E1 cells [3]. 6-keto-PGF(1alpha) release was increased in a concentration-dependent manner following LPS exposure (maximal at 10(-6)g/ml; EC(50) = 1 x 10(-9)g/ml), and was significantly inhibited by p38 MAPK blockade (reduced from 1.6+/-0.3 x 10(-9)g/ml to 4+/-1 x 10(-10)g/ml and 4+/-2 x 10(-10)g/ml with 10(-6) M SB203580 or 10(-6) M PD169316, respectively) [4].

Reference

[1]. Fu Y, et al. The p38 MAPK inhibitor, PD169316, inhibits transforming growth factor beta-induced Smad signaling in human ovarian cancer cells. Biochem Biophys Res Commun. 2003 Oct 17;310(2):391-7.
[2]. Nath R, et al. Inhibition of p38 kinase mimics survival signal-linked protection against apoptosis in rat cerebellar granule neurons. Cell Mol Biol Lett. 2001;6(2):173-84.
[3]. Kozawa O, et al. p38 MAP kinase is involved in the signalling of sphingosine in osteoblasts: sphingosine inhibits prostaglandin F(2alpha)-induced phosphoinositide hydrolysis. Cell Signal. 2000 Jul;12(7):447-50.
[4]. Brooks AC, et al. Endotoxin-induced activation of equine digital vein endothelial cells: role of p38 MAPK. Vet Immunol Immunopathol. 2009 Jun 15;129(3-4):174-80.