Date published: 2025-9-15

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SPHAR Inhibitors

Chemical inhibitors of SPHAR function by interfering with various signaling pathways and cellular processes that are crucial for the protein's activity. Staurosporine is a potent protein kinase inhibitor that can inhibit SPHAR through the prevention of its necessary phosphorylation events, which are vital for its activation. This disruption in phosphorylation status renders SPHAR inactive. Similarly, Bisindolylmaleimide I targets Protein Kinase C, which is often implicated in the phosphorylation of proteins like SPHAR. By obstructing this kinase activity, this chemical ensures that SPHAR remains in an unphosphorylated and inactive state. LY294002 and Wortmannin, both PI3K inhibitors, can inhibit SPHAR by disrupting the PI3K/Akt signaling pathway, which may be pivotal for SPHAR's activation. The activity of SPHAR can also be influenced by the MAPK/ERK pathway, where chemicals like PD98059 and U0126, both MEK inhibitors, prevent the activation of this signaling cascade, thus inhibiting any downstream effect on SPHAR.

Continuing with the MAPK pathway, LY3214996, an ERK1/2 inhibitor, can inhibit SPHAR by blocking the MAPK pathway, which might play a role in the regulation or activation of SPHAR. SB203580, which inhibits p38 MAP kinase, can also inhibit SPHAR by inhibiting upstream kinase activity within the MAPK pathway that SPHAR may depend on. Another kinase pathway involves the stress-activated kinase JNK, which is targeted by SP600125, inhibiting any JNK signaling required for SPHAR functionality. Rapamycin, an mTOR pathway inhibitor, can inhibit SPHAR if it is regulated by or interacts with the mTOR signaling pathway components. MG132 targets proteasomal degradation and can lead to the accumulation of ubiquitinated proteins, including those that regulate SPHAR, thereby inhibiting its function. Lastly, PF-477736, a Chk1 inhibitor, can inhibit SPHAR by interfering with cell cycle checkpoints and kinase signaling pathways that may involve SPHAR, thus affecting its cellular context and activity.

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