QSAR and molecular docking are integrated for the first time with experimental bioassay to guide rational design of mosquito repellents in a way similar to that widely used in drug discovery. The potential of the proposed integrated approach first tested on Aedes aegypti repellents will be applied in the future to the development of a broader class of vector control systems. Normalized and weighted values of the molecular fields are mapped on the molecular supergraph, with different shades of red and blue representing varying contributions, or Z-VAD-FMK impacts. These colorcoded schemes are given in Figure 5 for the atomic charge, van der Waals radii, hydrogen bond acceptor, hydrogen bond donor, and lipophilicity descriptors. Positions color-marked in more than one molecular field are the most informative ones. For example, a decrease in atomic charge and hydrophobicity coupled with an increase in van der Waals radius of the atom in position 2 leads to an increase in the antilog MED value. As it follows from the descriptor values given in Table 3, for the atoms occupying position 2, the terminal CH3 group is preferable both over the -CH2- group and a vacancy. This can be found useful for inferring an optimal length of alkyl chains. Similar analysis and conclusions can be made for position 86. The mosquito olfactory mechanism is complex, and OBP1 is most likely just the first step in developing a response. OBP1 either brings the odorant molecule into a direct contact with the olfactory receptors or exerts an allosteric action upon the OR. In both cases, the initial binding state of the AaegOBP1-odorant complex can change dramatically as the recognition event proceeds. It is quite reasonable to assume that the compounds sharing the 2-phenylcyclohexanol scaffold are bound in such a favorable mode that they are able to activate the OR machinery. FGF21 is expressed in multiple metabolic tissues. Moreover, FGF21 increases glucose uptake and insulin sensitivity while decreasing gluconeogenesis, lipogenesis and circulating cholesterol levels in multiple pre-clinical animal models when administered pharmacologically. Fasting and ketogenic conditions induce hepatic expression of FGF21 through PPAR��, while its expression is induced in adipose tissues by PPAR�� activation. FGF21 binds to fibroblast growth factor receptors complexed with the co-receptor ��Klotho and signals through phosphorylation cascades involving FRS2a and Erk/MAPK leading to transcriptional changes of several metabolic genes. Phosphorylation of Gsk-3, Shp2, Mek1/2, and Stat3 following FGF21 treatment of 3T3L1 adipocytes has been reported. There is growing evidence suggesting that FGF21 signaling specifically in adipose tissue is crucial for its beneficial metabolic effects. For example, FGFR1 and ��Klotho expression in adipose tissues, and downstream FGF21 signaling, are required for at least part of FGF21��s acute insulin-sensitizing and glucose uptake effects in mice. In support of this observation, FGF21 displays impaired glucose- and triglyceride-lowering efficacy in lipodystrophic mice. Recent reports have identified adiponectin as a key mediator of FGF21’s effects on glucose homeostasis and insulin sensitivity in mice. In addition, administration of FGF21 has been shown to induce weight loss and white adipose browning in several pre-clinical animal models. In order to further our VE-822 understanding of FGF21 signaling downstream of receptor activation in mouse adipose tissues, we have used unbiased transcriptomic and phosphoproteomic profiling to quantify transcripts and phosphoproteins that are modulated after acute FGF21 treatment. For our studies, we used both native FGF21 protein and a pegylated form that increases its half-life while displaying acute efficacy in terms of normalizing insulin-stimulated glucose uptake in insulin-resistant mice.