Multiple MCHR1 antagonists have also shown dose-dependent and sustained efficacy in chronic models of obesity (Kym et al., 2005; Souers et al., 2005a,b, 2007; Vasudevan et al., 2005a,b; Carpenter et al., 2006; Hertzog et al., 2006; Tavares et al., 2006a,b; Mendez-Andino and Wos, 2007; Mendez-Andino et al., 2007; Gehlert et al., 2009; Ito et al., 2009; Semple et al., 2009; Suzuki et al., 2009; Hadden et al., 2010; Mihalic et al., 2012; Sasmal et al., 2012a,b). This evidence concerns the gene MCHR1 and obesity due to melanocortin 4 receptor deficiency.