TMPRSS11E Inhibitors

Chemical inhibitors of TMPRSS11E, a serine protease of the Type II transmembrane serine protease (TTSP) family, act through various mechanisms to impede its proteolytic function. Aprotinin, AEBSF, Leupeptin Hemisulfate, 3,4-Dichloroisocoumarin, Phenylmethylsulfonyl fluoride (PMSF), SBTI (Soybean Trypsin Inhibitor), Antipain, Chymostatin, TLCK (Nα-Tosyl-L-lysine chloromethyl ketone hydrochloride), and TPCK (L-1-Tosylamido-2-phenylethyl chloromethyl ketone) are all primarily known to target the serine residue in the active site of TMPRSS11E. For instance, AEBSF and PMSF irreversibly modify the serine residue, rendering the protease inactive, while reversible inhibitors like Leupeptin Hemisulfate bind to this site transiently, substrate access. SBTI, a plant-derived inhibitor, and synthetic molecules like TLCK and TPCK, act similarly by occupying the active site, but TLCK and TPCK go a step further by covalently modifying the serine residue or adjacent amino acids critical for enzyme activity, thus exerting a more enduring inhibitory effect.

Pepstatin A and E-64, though not directly targeting TMPRSS11E, contribute to its inhibition by maintaining the stability and function of natural protease inhibitors within the cell, which can form complexes with TMPRSS11E and inhibit its function. Pepstatin A acts on aspartic proteases, while E-64 targets cysteine proteases; however, the consequence of their action promotes the inhibition of TMPRSS11E by increasing the population of active endogenous protease inhibitors. The complexity of TMPRSS11E inhibition is a result of the intricate balance between proteases and their inhibitors, and these chemicals play a pivotal role in modulating this balance. The specificity and mode of binding of these inhibitors are critical for their effectiveness, with irreversible inhibitors providing a sustained inhibition compared to the transient effects of reversible inhibitors.