TMEM167B Inhibitors

Chemical inhibitors of TMEM167B can affect the protein's function through various molecular pathways. Triciribine acts by inhibiting the phosphorylation and activation of AKT, a kinase involved in signaling pathways that regulate many cellular processes. When AKT phosphorylation is hindered, downstream effects like the functional activity of TMEM167B can be reduced, since its activity may rely on AKT-mediated signaling. Similarly, LY294002 and Wortmannin target the PI3K/AKT pathway, with LY294002 being a specific inhibitor of phosphoinositide 3-kinases (PI3K), and Wortmannin serving as a potent and irreversible inhibitor of the same. By suppressing PI3K activity, these inhibitors prevent the subsequent activation of AKT, leading to a decrease in TMEM167B activity if it is AKT-dependent. Rapamycin, another inhibitor, targets the mTOR pathway, which is downstream of AKT. It specifically inhibits the mTORC1 complex, potentially attenuating TMEM167B function if it is under the control of mTOR signaling.

Other inhibitors like Palbociclib, Olaparib, SB203580, PD98059, SP600125, U0126, MG132, and Bortezomib act on different aspects of cellular signaling and regulation. Palbociclib's selective inhibition of CDK4 and CDK6 can lead to a halt in cell cycle progression, which can indirectly affect TMEM167B if it is involved in cell cycle processes. Olaparib, as a PARP inhibitor, may inhibit TMEM167B by interfering with DNA repair mechanisms. SB203580 and SP600125, specific inhibitors of p38 MAP kinase and JNK respectively, alter stress response and apoptosis pathways, which can decrease TMEM167B activity if it is associated with these pathways. PD98059 and U0126 both act as MEK inhibitors, with the latter also blocking MAPK/ERK activation, potentially reducing TMEM167B function if it is reliant on this signaling cascade. Finally, proteasome inhibitors MG132 and Bortezomib can prevent the degradation of proteins, including TMEM167B, by the ubiquitin-proteasome system. If the function of TMEM167B requires its periodic degradation, the inhibition of this process would lead to the accumulation of TMEM167B, impacting its functional activity.