Ecdysone receptor

Ecclesiastical wines, 26 301 Ecdysone receptor agonists, 14 345 ECHIP JMP 4.0.4, features compared to other software, 8 398t ECLP tube press, 11 373 Eco-check Product excellence, 24 189 Eco-efficiency analysis, 24 189, 190 Eco-Efficiency program, 9 457 Ecological and Toxicological Association of Dyestuffs and Organic Pigments Manufacturers (ETAD), 9 234, 238 19 452... 

Antoniewski C., Laval M. and Lepesant J. A. (1993) Structural features critical to the activity of an ecdysone receptor binding site. Insect Biochem. Mol. Biol. 23, 105-14. 

Mu X, LeBlanc GA. 2004. Synergistic interaction of endocrine-disrupting chemicals model development using an ecdysone receptor antagonist and a hormone synthesis inhibitor. Environ Toxicol Chem 23 1085-1091. 

E, glutamate, glutamic acid EAE, experimental autoimmune encephalomyelitis EG, Enzyme Commission EGDY-R, ecdysone receptor... 

The ecdysone receptor belongs to the same subfamily of nuclear receptors as the liver X receptor LXR, the famesoid X receptor FXR and the vitamin D receptor VDR [8,[48]. All these receptors bind steroid-related compounds (oxysterol, bile acids and vitamin D). A detailed sequence alignment and a phylogenetic analysis encompassing 19 EcR protein sequences of various arthropods has been perfcxmed by Bonneton et al [46]. We will summarize here the main issues of this study. 

Nuclear receptors for the steroid hormone ecdysone in Drosophila deserve special consideration, for several reasons. First, the insect hormone ecdysone (Fig. 11.2) was the first steroid hormone shown to act at the level of the gene, because it induced puffs in the giant chromosomes of the fruitfly. Secondly, ecdysone activates the developmental programme of Drosophila, and, finally, the sequences of the DNA-binding domain (DBD) of the Drosophila nuclear ecdysone receptor and of receptor homologues (for example, the COUP-TFs chicken ovalbumin upstream promoter transcription factors) are highly conserved and nearly identical in vertebrates and humans. 

There are three ecdysone receptor isoforms ECR-A, ECR-Bl, and ECR-B2. All have identical DBDs and LBDs, but differ in the amino-terminal sequences. Functional... 

S.T. Suhr, E.B. Gil, M.C. Senut, F.H. Gage, High level transactivation by a modified Bombyx ecdysone receptor in mammalian cells without exogenous retinoid X receptor, Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 7999-8004. 

Structure-activity relationship for the activity of non-steroidal ecdysone agonists and the prediction of the ligand binding to the Bombyx mori ecdysone receptors (Y. Nakagawa, Kyoto Univ., Japan)... 

The SAR of the bisacylhydrazines, both during and after the discovery of the commercial compounds, has been extensively studied. This was partly driven by the novelty of the chemistry, mode of action (ecdysone agonists via interaction with the ecdysone receptor), and the availability of suitable assays (tissue, cell and target site based). Numerous papers have been published on this subject and the reader is referred to an excellent review by Dinan and Hormann [6] as a starting point. This section highlights and summarizes the collective findings by various researchers. 

However, the data to date indicate that lepidopteran ecdysone receptor affinities for methoxyfenozide and chromafenozide are most likely the primary drivers for their selective toxicity for lepidopteran larvae. 

While the very high affinities of tebufenozide, methoxyfenozide and chromafenozide for lepidopteran ecdysone receptors help explain the basis for their selective lepidopteran toxicity, the same does not apply to the fourth BAH insecticide, halofenozide, which is toxic to both lepidopteran and coleopteran larvae. Halofe-nozide has significantly reduced affinity for ecdysone receptors from the two insect orders. It seems that the relatively weak affinity of halofenozide to the ecdysone receptor of the target susceptible insect may be compensated by its increased metabolic stability in the same insect. 

At least two other chemotypes, tetrahydroquinolines (Fig. 25.1.5, 25 [87-88]) and amidoketones (Fig. 25.1.5, 26 [89, 90] also reviewed in Ref. [6]) have been shown to directly (ligand binding assays) or indirectly (cell based reporter gene transactivation assays) interact with the ecdysone receptor. These new ecdysone receptor binding chemistries could lead to new products for control of insect pests not controlled by current BAH insecticides. 

Fig. 25.1. S. Generalized structures of two additional chemotypes, tetrahydroquinolines (25) and amidoketones (26), that bind ecdysone receptors from several insects. X, Y, and Z represent different substitutions on the phenyl rings in the two chemotypes. R1 and R2 can be 4- or 5-attached carbons, either as two acyclic substituents or, preferably, as a five- or six-membered ring (reviewed in Ref. [6]).

Figure 3 shows an example of protein treatment with deuterated solvent for H/D exchange. The bovine albumin digest (Figure 3A) was treated directly on the MALDI sample plate as described above and a second spectrum was acquired (Figure 3B). Results of the PMF identification on the first spectrum querying the SWISS-PROT and TrEMBL databases for mammalian species allowed the identification of bovine albumin (ALBU BOVIN, P02769) at the first rank and Yellow mealworm ecdysone receptor (002035). In the case of bovine albumin, 10 peaks out of 22 were matched in both spectra (Table 7).

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