All docking was performed in Maestro by Schrödinger according to the "Covalent Docking for Virtual Screening and Pose Prediction" and "Introduction to Structure Preparation and Visualization" tutorials published by Schrödinger. Briefly, each compound was prepared using LigPrep to generate possible tautomers, conformations, and ionization states between pH 5-9. Structures for PTP1B (1KAK), SHP1 (4HJQ), SHP2 (6CMQ), and HePTP (3D42) were downloaded from the Protein Data Bank. These structures were prepared using the Protein Preparation Wizard to optimize charge, add hydrogens, and remove water molecules. All structures were aligned to PTP1B (1KAK), and the receptor grid box for docking calculations was centered on the co-crystalized ligand in 1KAK. Covalently docked complexes were generated using the CovDock module in the Pose Prediction docking mode, and the top scoring complex for each compound was selected as a representative pose for further structural analysis. NHS. M.J. is funded by the NIH (R35GM128802; R01AG071869 and R01HG012216) and NSF (Award 2224211). Experiments involving cryoprobe NMR data were supported by funding from the NIH Office of the Director (award # S10OD026749). SYX is supported by a Barry Goldwater Scholarship. LCT is supported by an NSF Graduate Research Fellowship (award # 2036197). CAC is supported by an NSF Graduate Research Fellowship.