Sec63 Inhibitors

Sec63 inhibitors belong to a distinct chemical class that exerts their influence on cellular processes through the modulation of the Sec63 protein. Sec63 is a crucial component of the endoplasmic reticulum (ER) translocon, an intricate machinery responsible for the translocation and proper folding of nascent polypeptides entering the ER lumen. The Sec63 protein functions as a co-chaperone, working in collaboration with BiP (Binding Immunoglobulin Protein) to facilitate protein folding, quality control, and translocation across the ER membrane. By inhibiting the activity of Sec63, these compounds disrupt the finely tuned processes of protein maturation within the ER.

Sec63 has profound implications for cellular homeostasis, as it disrupts the delicate balance required for the synthesis and processing of proteins. Sec63 inhibitors typically act by binding to specific regions of the Sec63 protein, impeding its normal function and leading to the accumulation of misfolded or unfolded proteins. This disruption triggers cellular stress responses, such as the unfolded protein response (UPR), as the cell attempts to rectify the imbalance. The consequences of Sec63 inhibition extend beyond protein folding; they can impact ER-associated degradation pathways and contribute to the accumulation of unfolded proteins, potentially eliciting a cascade of cellular events.