ADAM26B Inhibitors

Chemical inhibitors of ADAM26B function primarily by engaging with the metalloprotease domain that is central to the protein's enzymatic activity. Marimastat and Batimastat, for instance, are broad-spectrum matrix metalloprotease inhibitors that target this domain. By chelating the zinc ion within the active site of ADAM26B, these inhibitors prevent the catalytic process required for the proteolysis of substrate molecules. Similarly, Ilomastat binds to the same zinc-containing active site, obstructing the enzymatic function of ADAM26B. This mode of inhibition is not exclusive to these compounds; Prinomastat and PD 166793 also engage ADAM26B in a comparable manner, targeting the metalloprotease domain to suppress the protein's protease function. The inhibition of this proteolytic activity is critical to modulating the enzymatic process ADAM26B undertakes.

Other chemical inhibitors such as TAPI-0 and Doxycycline, despite their primary uses in different biochemical contexts, can also inhibit ADAM26B. TAPI-0, known for its inhibition of tumor necrosis factor-alpha converting enzyme (TACE), a similar metalloprotease, can inhibit ADAM26B by a shared mechanism of metalloprotease inhibition. Doxycycline, although classified as an antibiotic, has been noted to bind the metalloprotease domain and impede ADAM26B's activity. Further along this spectrum, SB-3CT, which selectively targets MMP-2 and MMP-9, can inhibit ADAM26B by a substrate transition state mimicry that blocks the active site. In addition, compounds like Andrographolide, which inhibits NF-kB activation - a regulator of various MMPs - can lead to a reduction in ADAM26B's proteolytic activity. ARP-100, Ro 32-3555, and WAY-170523 are other examples of MMP inhibitors that can bind directly to the metalloprotease domain of ADAM26B, thereby preventing the proteolytic cleavage of ADAM26B's substrates and effectively inhibiting its action. These inhibitors utilize the common strategy of active site blockade to impede the enzyme's function.