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Being an inhibitor to JNK, SP600125 controls the stress activated response within the cells. Inflammatory diseases are generally the outcome of external stimuli like shock, bacterial endotoxin, hypoxia and UV radiation. During these diseases the immune proteins are expressed to a large extent. The expression of multiple genes is controlled by few transcription factors. Hence the signaling pathways which control these transcription factors are therapeutically very important. AP-1 is a transcription factor which is associated with DNA and regulates the expression a large number of genes. C-Jun is a component of AP-1 complex. JNK activated c-Jun by phosphorylation. Hence JNK indirectly controls the expression of a large number of genes like cytokines, growth factors, immunoglobulins and matrix metalloproteinases. The structure of SP600125 is derived from anthrapyrazolone and makes all the three isoforms of JNK (JNK1/2/3) its target [1]. MECHANISM OF ACTION OF SP600125 SP600125 competes with ATP for its binding site within JNK. It is 20 times more specific in its action when compared with other kinases. It checks the activation of c-Jun in a dose dependent manner. The expression of the following genes - IFN-?, COX-2, IL-2 and TNF-? is controlled by this inhibitor. This prevents the differentiation of CD4 cells within human beings. During animal studies it blocked the expression of TNF-? and inhibited the apoptosis of CD8+ and CD4+ thymocytes. Due to its efficient action against JNK it is able to control cancer, inflammatory disorders and apoptosis [1]. SP600125 HELPS IN THE ANALYSIS OF TNF- ? INDUCED APOPTOSIS To study the effect of neuronal degeneration, PC12 cells were used as a model. Differentiated PC12 cells were found to be more subjective to apoptosis in comparison to naïve cells. Confocal microscopy was used to analyze TNF-? induced apoptosis within both the cells. During this kind of apoptosis Bax gets translocated to mitochondria and cytochrome C is released from mitochondria within differentiated PC12 cells. SP600125 did not act as an apoptosis inhibitor in this particular case. However inhibitors of caspase 8, inhibited this apoptosis efficiently. SP600125 inhibited the translocation of BAX to mitochondria (the initial step of TNF-? induced apoptosis) [2]. DIHYDROARTEMISININ-DEPENDENT APOPTOSIS ENHANCED BY SP600125 JNKs are the members of MAPK family which plays a significant role in apoptotic pathways. JNK activates Bax protein either directly or indirectly and stimulated mitochondria induced apoptosis. The proapoptotic protein Bcl-2 also gets stimulated under the action of JNK. A high throughput screening of the chemical library led to the discovery of SP600125. Due to its specific action this inhibitor became the choice to inhibit various biological processes. DHA or dihydroartemisinin stimulates the activation of Bax. SP600125 enhances this activation further and stimulates the process of apoptosis [3]. SP600125 IS AN ANTAGONIST TO ARYL HYDROCARBON RECEPTOR Generally AhR ligands are planar and aromatic in nature. These ligands affect the function of AhR differently. ?-naphthoflavone acts as an agonist and activates the function of AhR. On the other hand LY294002 is derived from flavonoid and acts as an antagonist to AhR. It inhibits the action of AhR. When TCDD (agonist to AhR) and another inhibitor are administered together into MCF10A-Neo cells, it led to the suppression of CYP1A1 expression. SP600125 was used in this study and determines the role of JNK during this suppression. The final results showed that SP600125 acts like an antagonist to AhR. It also controlled the stimulation of CYP1A1 by agonist TCDD. CONCLUSION In summary, SP600125 specifically inhibits different isoforms of JNK and hence controls the prognosis of various disorders. It regulates the expression of large number of genes via its inhibitory action on JNKs. We has established long-term and stable relationships with more than 10,000 customers from pharmaceutical and biotech companies, universities and research institutions. We have high quality inhibitors like HKI-272, GSK690693, av-951 & more. We have headquarters in both United States and Europe, and also has 38 distributors worldwide. We provide overnight delivery in North America and Europe.
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SP600125, apoptosis inhibitor, LY294002,
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