With the application of machine learning in drug design and optimization (Ekins et al., 2019; Kaiser et al., 2020; Walters and Barzilay, 2021), identifying a series of new compounds that were simultaneously optimized for on-target potency (e.g., Fgr, Hck, Abl) and off-target safety (e.g., Lyn) will provide more promising solutions for the pharmacological intervention of obesity-related metabolic disorders. This evidence concerns the gene HCK and obesity due to melanocortin 4 receptor deficiency.