Date published: 2025-9-13

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SPRED3 Inhibitors

Chemical inhibitors of SPRED3 operate by targeting different components of the signaling pathways in which the protein is involved. PD98059 and U0126 are both selective inhibitors of MEK, a kinase that functions upstream of ERK in the Ras/Raf/ERK pathway, which is negatively regulated by SPRED3. By preventing the phosphorylation and activation of ERK, these inhibitors could lead to a reduction in the regulatory effects of SPRED3 on the pathway. LY294002 and Wortmannin are inhibitors of PI3K, a key player in the Akt pathway that is known to interact with the Ras/Raf/ERK pathway. The inhibition of PI3K by these chemicals could therefore diminish the downstream signal that contributes to the regulation by SPRED3. Rapamycin, by inhibiting mTOR, a downstream effector of PI3K/Akt signaling, can also indirectly suppress the activity within the ERK pathway, thereby inhibiting the function of SPRED3.

Moreover, SB203580 and BIRB 796 are inhibitors of p38 MAP kinase, another MAP kinase pathway that can affect the dynamics of the ERK pathway. Through their action, they could lead to changes in the signaling cascade, resulting in the functional inhibition of SPRED3. SP600125, which inhibits JNK, can also decrease signaling through the ERK pathway, thereby inhibiting SPRED3. SL327 and PD0325901, both selective inhibitors of MEK, serve to prevent the activation of ERK, further inhibiting the regulatory effects SPRED3 has on this pathway. Lastly, Sorafenib and Sunitinib target multiple tyrosine protein kinases, such as VEGFR and PDGFR, and serine/threonine kinases like Raf-1 and BRAF. By suppressing the activity of these kinases, these inhibitors can downregulate the Ras/Raf/ERK pathway's activity, leading to the functional inhibition of the regulatory role SPRED3 plays within this pathway.

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