Inhibitor compounds and agents of Cathepsin C, CELA1, CELA3A and/or structurally related molecules thereto, compositions comprising the same, and uses thereof in the inhibition and/or prevention of cell and/or tissue necrosis are described. The compounds include imidazoles of Formula VI:






wherein G1 is pyrrolidine, pyrazolidine, imidazolidine piperidine, or piperazine and G2 is alkyl, cycloalkyl, heterocycle, or aryl. The pyrrolidine, pyrazolidine, imidazolidine, piperidine, or piperazine of G1 and the alkyl, cycloalkyl, heterocycle, or aryl of G2 are optionally substituted with one or more substituents independently selected from the group consisting of halogen, NO2, CN, C1-C6 alkyl, C1-C6 haloalkyl, NH2, OH, OC1-C6 alkyl, C(O)H, C(O)C1-C6 alkyl, C(O)NH2, C(O)OH, and C(O)OC1-C6 alkyl. Variations applications for the described compounds, and combination therapies are further described as well.