Date published: 2025-9-17

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GIMAP8 Inhibitors

Chemical inhibitors of GIMAP8 function by disrupting the signaling pathways that are essential for its activity and stability. Wortmannin and LY294002 are both potent inhibitors of phosphoinositide 3-kinases (PI3K), which play a pivotal role in intracellular signaling. By inhibiting PI3K, these chemicals prevent the phosphorylation and activation of downstream targets involved in cell survival, which is integral to the function of GIMAP8. Similarly, U0126 and PD98059 target MEK1/2 and MEK respectively, which are upstream regulators of the extracellular signal-regulated kinase (ERK) pathway. Inhibition of these kinases results in reduced ERK pathway activity, which can affect the regulation of GIMAP8. Additionally, SB203580 and SP600125 obstruct the MAPK pathway by selectively inhibiting p38 MAPK and c-Jun N-terminal kinase (JNK), respectively. These kinases are involved in cellular responses to stress and cytokines, and their inhibition can change the cellular environment in which GIMAP8 operates.

Continuing with this theme of pathway interference, Rapamycin specifically inhibits the mammalian target of rapamycin (mTOR), a kinase that is central to cell growth and metabolism signaling. This inhibition can perturb the processes in which GIMAP8 is involved. PP2, on the other hand, inhibits Src family kinases, which are implicated in various signaling pathways, including those that intersect with the regulatory mechanisms of GIMAP8. BAY 11-7082 disrupts the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, which is crucial for cell survival signals that GIMAP8 may rely on. LY3214996 specifically inhibits ERK1/2, thus affecting the MAPK signaling pathway, which is involved in cell proliferation and survival, and consequently the function of GIMAP8. Lastly, PF-562271 and Dasatinib target focal adhesion kinase (FAK) and Src family kinases along with BCR-ABL, respectively. The inhibition of these kinases by PF-562271 can affect cellular adhesion and migration processes, while Dasatinib's broad-spectrum activity can alter multiple signaling pathways, both of which are important for the regulation of GIMAP8's activity within cells.

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