A 2015 review by Johansson and Löfberg (2015) offered the expert opinion that (at the time of publication) “the target [MCHR1] has not been conclusively evaluated,” and that these various “clinical failures have been associated with far from ideal compound properties.” This situation likely stems from several persistent issues that drug designers faced in the development of MCHR1 antagonists for obesity. Here, MCHR1 is linked to obesity due to melanocortin 4 receptor deficiency.