ADAM26 Inhibitors

Chemical inhibitors of ADAM26 employ various mechanisms to obstruct its protease functions. Marimastat and Batimastat, for instance, function by engaging with the metalloprotease domain of ADAM26, which is critical for its substrate cleavage capability. These inhibitors form a bond with the active site, where they chelate the zinc ion, an essential cofactor for the enzymatic activity of ADAM26. This binding impedes the ability of ADAM26 to interact with its substrates, thus inhibiting its function. Similarly, Ilomastat and GM6001 target the same active site, using their chemical structure to interact with the zinc ion, which is paramount for the catalytic action of ADAM26. By occupying this site, these inhibitors prevent ADAM26 from performing its physiological role of proteolytic processing of substrates.

Further, TAPI-1 and Prinomastat are known to directly inhibit the protease activity of ADAM26 by inserting themselves into the enzyme's active site, blocking access to substrates that would normally be processed by ADAM26. SB-3CT's inhibition mechanism, extrapolated from its known effects on gelatinases, similarly inhibits the protease domain of ADAM26, suggesting a broad-spectrum mechanism that encompasses the inhibition of this protein's function. WAY-170523 and PD166793 bind to the catalytic domain of ADAM26, offering a steric hindrance that precludes substrate interaction with the enzyme. GI254023X operates by occupying the enzyme's active site as well, effectively inhibiting the metalloprotease activity of ADAM26. Lastly, Ro 32-3555 inhibits ADAM26 by binding to its active site and preventing substrate interaction. Through these interactions, these chemicals ensure the functional inhibition of ADAM26, restricting its normal biological activity.