https://www.selleckchem.com/products/ly2606368.html Using an optimized procedure, we further assessed 132 potential neurotoxins that spanned a wide range of molecular targets, many of which were previously detected in environmental waterbodies. The distinct altered behavioral barcodes indicated that the spontaneous movement was impacted by diverse neuroactive substances, and the effects could be effectively evaluated with the developed assay. The web-based tool, named EMAnalysis, is further provided at http//www.envh.sjtu.edu.cn/zebrafish_contraction.jsp. Thus, this assay provides an efficient platform to accelerate the pace of neurotoxic environmental contaminant discoveries.The melanocortin receptors (MCRs) are important for numerous biological pathways, including feeding behavior and energy homeostasis. In addition to endogenous peptide agonists, this receptor family has two naturally occurring endogenous antagonists, agouti and agouti-related protein (AGRP). At the melanocortin-4 receptor (MC4R), the AGRP ligand functions as an endogenous inverse agonist in the absence of agonist and as a competitive antagonist in the presence of agonist. At the melanocortin-3 receptor (MC3R), AGRP functions solely as a competitive antagonist in the presence of agonist. The molecular interactions that differentiate AGRP's inverse agonist activity at the MC4R have remained elusive until the findings reported herein. Upon the basis of homology molecular modeling approaches, we previously postulated a unique interaction between the D189 position of the hMC4R and Asn114 of AGRP. To further test this hypothesis, six D189 mutant hMC4Rs (D189A, D189E, D189N, D189Q, D189S, and D189K) were generated and pharmacologically characterized resulting in the discovery of differences in inverse agonist activity of AGRP and an 11 macrocyclic compound library. These data support the hypothesized interaction between the hMC4R D189 position and Asn114 residue of AGRP and define critical ligand-recep