Abstract: The present disclosure provides compounds according to Formula I and pharmaceutically acceptable salts thereof, as well as compositions including such compounds and a pharmaceutically acceptable carrier or excipient. Further provided are methods of inactivating SIRT6 with compounds of Formula I as well as compounds of Formula III, W2—R2—Y—R3, as described herein. In addition, the present technology provides methods of treatment using such compounds to lower LDL levels, lower triglyceride levels, and/or increase glucose tolerance in a subject, and/or to inhibit proliferation of ovarian, colorectal, hepatocellular, non-small cell lung, glioblastoma, osteosarcoma, pancreatic, and skin cancer cells, and/or inhibit liver and/or kidney fibrosis, and/or promote corneal epithelial wound healing.