152121-53-4

Usage

Uses

1. Used in Cancer Research:
PD 169316 is used as an inhibitor of p38 MAP kinase for studying the role of this enzyme in cancer cell signaling and growth. It is particularly effective in inhibiting TGFβ-induced Smad signaling in human ovarian cancer cells, which can provide insights into the development and progression of the disease.
2. Used in Cardiology:
PD 169316 is used as a therapeutic agent to reduce myocardial ischemia/reperfusion induced VDAC phosphorylation, which can help in the treatment and management of heart-related conditions.
3. Used in Cell Signaling Studies:
PD 169316 is used as a research tool to investigate the role of p38 MAPK in various cellular processes, including apoptosis and cell survival, by selectively inhibiting the enzyme.
4. Used in Pharmaceutical Development:
PD 169316 is used as a lead compound in the development of new drugs targeting p38 MAPK and related signaling pathways, with potential applications in treating various diseases, including cancer and cardiovascular conditions.
5. Used in Cell Culture:
PD 169316 has been used in culture media to promote embryoid bodies differentiation, which can be beneficial for studying early stages of development and cellular differentiation processes.
6. Used in Hepatocyte Research:
PD 169316 has been used for the inhibition of p38 enzyme in human hepatocytes, which can help in understanding the role of this enzyme in liver function and disease.

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.

Upstream product

• 586-95-8 pyridine-4-methanol 
• 555-16-8 4-nitrobenzaldehdye 
• 403-43-0 4-fluorobenzoyl chloride 
• 152122-41-3 2-(tert-butyldimethyl-silyloxy)-1-(4-fluorophenyl)-2-pyridin-4-yl-ethanone 
• 117423-41-3 4-((tert-butyldimethylsilyloxy)methyl)pyridine 
• 116332-54-8 4-fluoro-N-methoxy-N-methylbenzamide 

Downstream Products

• 152121-54-5 2-(4-Aminophenyl)-4-(4-fluorophenyl)-5-(pyridin-4-yl)-1H-imidazole 

Relevant academic research and scientific papers

Triarylimidazoles

Compounds of formula (I) or a pharmaceutically acceptable salt thereof: wherein R1, R2and R3are various substituent groups; and one of X1and X2is N or CR′, and the other is NR′ or CHR′ wherein R′ is hydrogen, OH, C1-6alkyl, or C3-7cycloalkyl; or when one of X1and X2is N or CR′ then the other may be S or O; and their use as pharmaceuticals.

Treatment for CNS injuries

The present invention is directed to the use of 2,4,5-trisubstituted imidazole compounds and compositions in the treatment of CNS injuries to the brain.

Use of kinase inhibitors for treating neurodegenerative diseases

The present invention relates to methods of treating neurodegenerative diseases, including but not limited to Parkinson's disease. In particular, the present invention provides methods utilizing the administration of pyridyl imidazoles having simultaneous inhibitory activity towards p38 mitogen-activated protein (MAP) kinase and c-jun-N-terminal kinase (JNK). The present invention also provides methods for preventing apoptosis of dopamine neurons using pyridyl imidazoles. The present invention also provides methods for the treatment of neurodegenerative diseases, including but not limited to Parkinson's disease.

Pyrimidinyl imidazoles

Novel 2,4,5-triaryl imidazole compounds and compositions for use in therapy.

Regulation of stress-induced cytokine production by pyridinylimidazoles inhibition of CSBP kinase

Members of three classes of pyridinylimidazoles bind with varying affinities to CSBP (p38) kinase which is a member of a stress-induced signal transduction pathway. Based upon SAR and protein homology modeling, the pharmacophore and three potential modes of binding to the enzyme are presented. For a subset of pyridinylimidazoles, binding is shown to correlate with inhibition of CSBP kinase activity, whereas no significant inhibition of PKA, PKα and ERK kinase activity is observed.

Imidazole derivatives and their use as cytokine inhibitors

As cytokine inhibitors 2,4,5-triarylimidazole compounds and compositions for use as cytokine inhibitors.

Pyridyl imidazoles

Novel 2,4,5-triaryl imidazole compounds and compositions for use in therapy.