Finally, we hypothesized that more diversity among the NGT compounds compared to HE compounds translated into better selectivity for MC2R in the MCXR family (Fig ). Designing a selective agonist or antagonist for MC2R is important and challenging because ACTH also activates all other MCXRs . In a single concentration functional assay panel, NGT compound ATMW-7 demonstrated 10-fold or better selectivity for MC2R over MC1R, MC4R, and MC5R (Figure , Methods). Highlighting the challenges in finding selective antagonists, no other compound demonstrated selectivity exceeding 10-fold for even one of the family members, with the exception of ATMW-6 (10.3-fold for MC5R). Altogether, four compounds were at least 3-fold selective.