Chemical inhibitors of IEX-1L interfere with various signaling pathways that contribute to the regulation of this protein. SB-203580 operates by targeting p38 MAP kinase, a critical enzyme in the pathway that activates transcription factors for IEX-1L expression. When SB-203580 inhibits p38 MAP kinase, the activation of these transcription factors is decreased, leading to lower expression levels of IEX-1L. Similarly, SP600125 suppresses the activity of IEX-1L by inhibiting c-Jun N-terminal kinase (JNK), another kinase involved in stress-related signaling pathways that affect IEX-1L. LY294002 and Wortmannin both inhibit phosphoinositide 3-kinase (PI3K), a molecule that plays a significant role in the PI3K/Akt signaling pathway, which is known to regulate IEX-1L. The inhibition of PI3K by these chemicals results in reduced activity of downstream signaling components that would normally increase IEX-1L activity.
PD98059 and U0126 are both selective inhibitors of mitogen-activated protein kinase kinase (MEK), which is upstream of extracellular signal-regulated kinases (ERK) implicated in the regulation of IEX-1L. By inhibiting MEK, these chemicals reduce the activation of ERK, subsequently diminishing the functional activity of IEX-1L. Rapamycin, on the other hand, inhibits the mammalian target of rapamycin (mTOR), another key kinase in the PI3K/Akt pathway, resulting in decreased regulation of IEX-1L. PP2 targets Src family kinases, which are part of multiple signaling pathways that intersect with IEX-1L regulation. The action of PP2 leads to a reduction in IEX-1L activity. Stattic, by inhibiting STAT3, affects the transcriptional level of IEX-1L, while NSC 23766 inhibits Rac1, a GTPase that influences the pathways regulating IEX-1L, leading to a decrease in its signaling. Lastly, Triptolide and BAY 11-7082 both target NF-κB, a transcription factor involved in the regulation of IEX-1L. Inhibition of NF-κB by these chemicals results in a decrease in IEX-1L's functional activity.
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