CPN reg Inhibitors

Alsterpaullone inhibits cyclin-dependent kinases (CDKs), which are vital for cell cycle regulation. By inhibiting CDKs, this chemical can disrupt the cell cycle and therefore inhibit the function of CPN reg, which is involved in the regulation of protein folding during the cellular stress response that often accompanies cell cycle progression.

Thapsigargin inhibits the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA), leading to depletion of calcium stores in the endoplasmic reticulum (ER). CPN reg, a chaperone, is sensitive to calcium levels in the ER, and disruption of calcium homeostasis can inhibit its protein folding and stress response functions, as these processes are calcium-dependent.

Tunicamycin inhibits N-linked glycosylation in the ER. Since CPN reg is involved in the folding of glycoproteins, inhibition of glycosylation can lead to an accumulation of misfolded proteins, which can overwhelm CPN reg functions and inhibit its chaperone activity by increasing the demand beyond its functional capacity.

Eeyarestatin I inhibits the p97 ATPase and associated deubiquitinating enzymes, which are involved in the endoplasmic-reticulum-associated degradation (ERAD) pathway. CPN reg works in conjunction with the ERAD pathway to refold or degrade misfolded proteins. Inhibition of this pathway can lead to an overload of misfolded proteins that CPN reg cannot manage, thereby inhibiting its function.

Bortezomib inhibits the 26S proteasome, which is responsible for degrading ubiquitinated proteins. The accumulation of ubiquitinated proteins due to proteasome inhibition can indirectly inhibit CPN reg by overwhelming its ability to assist in protein folding, leading to an increased protein misfolding burden within the cell.

MG-132 is another proteasome inhibitor that, by blocking the degradation of ubiquitinated proteins, can lead to an accumulation of misfolded or damaged proteins within the cell. This accumulation indirectly inhibits CPN reg by increasing the workload on the protein folding machinery, potentially overwhelming CPN reg's functional capacity.

Cyclopiazonic Acid is an inhibitor of the SERCA pump, like Thapsigargin, and disrupts calcium homeostasis in the ER. The inhibition of calcium regulation can affect CPN reg's ability to properly fold proteins by altering the calcium-dependent chaperone environment in which CPN reg operates, leading to functional inhibition.

Salubrinal selectively inhibits dephosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α). Phosphorylated eIF2α is a response to ER stress, which CPN reg helps to alleviate by chaperoning misfolded proteins. By preventing the dephosphorylation of eIF2α, Salubrinal can lead to an overactivation of the stress response, potentially overburdening CPN reg's chaperoning capacity.

Guanabenz, like Salubrinal, also prolongs the phosphorylation of eIF2α, which is implicated in the unfolded protein response (UPR). CPN reg's functions are part of the UPR, and its inhibition can occur through the constant activation and overwhelming of the UPR pathway, which can lead to an excess of misfolded proteins that CPN reg is unable to manage.

Pifithrin-μ inhibits the function of heat shock protein 70 (HSP70), which works synergistically with CPN reg in protein folding and stress response. Inhibition of HSP70 can indirectly lead to the inhibition of CPN reg by increasing the pool of misfolded proteins and overwhelming CPN reg's functional capacity within the chaperone network.