All authors are current or former employees of subsidiaries of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co. Inc., Rahway, NJ, USA and may own stock or stock options in Merck & Co. Inc., Rahway, NJ, USA. Figure S1. H&E and IHC staining of in vitro epidermal skin organotypic culture. Figure S2. Western blot and qPCR analysis of SPINK5, KLK5, and KLK7 expression. Figure S3. Structure of cyclic depsipeptides and amino acid sequences of soybean trypsin inhibitors. Figure S4. Enzymatic activity assays of recombinant KLK5 and KLK7 to evaluate the potency of compounds. Data S1. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.