BRI3 Inhibitors

Chemical inhibitors of BRI3 can modulate the protein's activity through diverse mechanisms of action by targeting various signaling pathways in which BRI3 is involved. Wortmannin and LY294002, both phosphoinositide 3-kinase (PI3K) inhibitors, can lead to a reduction in AKT signaling, a pathway upstream of BRI3. The inhibition of PI3K by these compounds can result in decreased AKT activation, which is essential for the phosphorylation and subsequent activation of proteins that are regulated by AKT, including BRI3. Similarly, Dasatinib and PP2 function by selectively inhibiting Src family kinases. The activity of BRI3 can be attenuated when these kinases are inhibited because BRI3 is linked to signaling pathways incorporating Src family kinase activity. Reduced activation of these kinases can lead to a decrease in the functional activity of BRI3, which may rely on Src signaling for its role within the cell.

Further regulating the activity of BRI3, U0126 and PD98059 target the MAPK/ERK pathway by inhibiting MEK1/2. The inhibition of MEK disrupts the phosphorylation and activation of ERK, a kinase that can control the function of BRI3. SB203580 and SP600125 inhibit other MAPK family members, namely p38 MAPK and JNK, respectively. BRI3 activity that depends on signaling through these MAPK pathways can be inhibited when p38 MAPK or JNK activation is blocked. Additionally, GF109203X and Go6983, inhibitors of protein kinase C (PKC), can alter BRI3 activity by impeding PKC-mediated signaling pathways. The inhibition of PKC can therefore lead to a decrease in BRI3 functionality if its activity is regulated by PKC-dependent processes. Lastly, mTOR pathway inhibitors such as Rapamycin and AZD8055 can suppress the functional activity of BRI3 by targeting mTORC1 and mTORC2 complexes. Inhibition of mTOR signaling can affect BRI3 if its activity is interwoven with mTOR-dependent cellular processes.