DPP3 Inhibitors

Chemical inhibitors of DPP3 include a range of compounds that can indirectly influence the protein's activity by interacting with various biochemical pathways and cellular processes. Zinc Pyrithione, for example, targets metalloproteases by disrupting metal ion homeostasis, which is crucial for metalloproteins like DPP3. This disruption can inhibit the catalytic activity of DPP3 by altering the metal environment necessary for its function. Similarly, Ebselen, through its redox properties, can interact with thiol groups or essential metal ions at the active sites of enzymes. By doing so, it alters the enzyme activity, potentially leading to the inhibition of DPP3's function. Oltipraz can lead to increased cellular glutathione levels, which may interfere with the redox state of the cell and, consequently, the redox-dependent catalytic activity of DPP3. Disulfiram, known for its ability to chelate metal ions, can bind to DPP3's metal cofactors, thereby inhibiting its metalloenzyme activity.

The inhibition of kinase signaling pathways also plays a role in regulating DPP3 activity. PD 98059 and U0126 are inhibitors of MEK, which ultimately leads to reduced ERK phosphorylation. Since DPP3 activity can be regulated by phosphorylation, the inhibition of upstream kinases by these compounds can decrease DPP3 activation. LY294002, an inhibitor of PI3K, can alter cellular signaling that may lead to changes in DPP3 function. The inhibition of p38 MAP kinase by SB203580 can modify cellular responses to stress and inflammation, indirectly affecting DPP3 activity. Similarly, SP600125 inhibits JNK, which is involved in pathways regulating inflammation and apoptosis, processes that can modulate protease function and, in turn, affect DPP3 activity. Auranofin, by inhibiting thioredoxin reductase, changes the cellular redox state, which may lead to the inhibition of redox-sensitive enzymes like DPP3. Apocynin suppresses NADPH oxidase, thereby potentially reducing ROS levels and influencing the function of enzymes like DPP3 that are sensitive to redox changes. Lastly, NS-398, a COX-2 inhibitor, can alter prostaglandin levels, influencing various signaling pathways that regulate enzyme activity, including that of DPP3. Each of these compounds interacts with specific cellular components or pathways that are integral to the proper functioning of DPP3, leading to its inhibition.