DSSTox (NCTRER) National Center for Toxicological Research Estrogen Receptor Binding Database
Researchers within FDA's National Center for Toxicological Research (NCTR) generated a database of experimental estrogen receptor binding results for the express purpose of developing improved QSAR models to predict ER binding affinities.The NCTR ER database is a structurally diverse set of natural, synthetic, and environmental estrogens covering most known estrogenic classes and spanning a wide more ..
BioActive Compounds: 131
Researchers within FDA's National Center for Toxicological Research (NCTR) generated a database of experimental estrogen receptor binding results for the express purpose of developing improved QSAR models to predict ER binding affinities.The NCTR ER database is a structurally diverse set of natural, synthetic, and environmental estrogens covering most known estrogenic classes and spanning a wide range of biological activity. It represents the largest published ER binding database of same-assay results generated in a single laboratory. The NCTR ER database consists of 232 chemicals (131 active and 101 inactive) selected a priori based on structural characteristics and tested in a well validated and standardized in vitro rat uterine cytosol ER competitive-binding assay [see NCTRER refs]. Information on the percent purity and purchasing source for all chemicals are not included in the DSSTox SDF, but can be obtained from the original NCTR ER Source database and Main Citations listed below. The main citation (Fang et al., 2001) surveys the NCTR ER database from a chemical class based, structure-activity relationship (SAR) perspective. Qualitative SAR characteristics of the NCTR ER database are discussed and a set of general hierarchical rules for identifying potential estrogens are presented. The DSSTox NCTRER SDF augments the original NCTR ER database with chemical class and SAR information abstracted from Fang et al. (2001). The DSSTox SDF file supplements the measured ER relative binding affinity for each chemical (ER_RBA) with chemical class assignment to one of 6 major estrogenic classes further divided into 20 subclasses (ChemClass_ERB), along with a qualitative activity measure, ActivityCategory_ER_RBA. A brief narrative SAR rationale pertaining to ER RBA patterns observed by Fang et al. (2001) for each of the 20 subclasses within the database are provided in the field, ActivityCategory_Rationale_ChemClass_ERB. The original NCTR ER database, from which the expanded DSSTox NCTRER was formed, is contained within a larger Endocrine Disruptor Knowledge Base (EDKB) accessible from the FDA Source Website. That website provides online access to a relational database comprised of in vitro and in vivo experimental data for about 2000 natural and synthetic compounds, much of this extracted from the literature and representing testing in many laboratories. Data are included for biological assays that measure estrogenic and androgenic activity. Estrogenic endpoints include in vitro assays for estrogen receptor competitive binding affinity, cell proliferation, and reporter-gene assays, and in vivo assays for uterotrophic activity (i.e., uterine weight gain and vaginal cornification). The database also contains a bibliography of over 1200 citations, many of which include abstracts.
Estrogen receptor relative binding affinity is determined using a competitive receptor binding assay as described in NCTRER Ref (Blair et al., 2000). Briefly, a chemical competes with radiolabeled E2 (i.e., estradiol) for binding to the ER in rat uterine cytosol and the concentration of chemical that causes 50% inhibition of E2 binding (i.e., IC50) is measured. The ER_RBA is calculated by dividing the IC50 of E2 (9X10-10M) by the IC50 of the competitor and multiplying by 100 (E2 RBA = 100). The validated assay tested 1nM E2 with concentrations of competitor ranging from 1nM to 1mM. The larger the ER_RBA values, the greater the binding affinity; ER_RBA > 100 means compound has greater binding affinity than natural ER ligand, E2. ER_RBA = 0 when no activity or 50% inhibition was not reached (designated either inactive or slight binder). Activity Outcome based on reported ER_RBA: "active" = ER_RBA >1E-5; "inconclusive" = max< 50% inhibition or ER_RBA< 1E-5, i.e. slight binder; "inactive" = 0, i.e. no activity. Activity Score is mapping of LOG_ER_RBA values (ER-RBA>1E-5), spanning activity range [MIN, MAX] onto Integer 20-100 Activity range, where 100 is highest potency and 20 is lowest active potency. If Activity Outcome is "active": Activity Score = 80 * INTEGER[(LOG_ER_RBA - MIN)/(MAX # MIN)]. If Activity Outcome is "inconclusive" (i.e., slight binder): Activity Score = 5. If Activity Outcome is "inactive" (i.e., no activity): Activity Score = 0
DSSTox (NCTRER): National Center for Toxicological Research Estrogen Receptor Binding Database
To access complete SD file and documentation, refer to the DSSTox NCTRER Download Page
For more information and description pertaining to this assay, see NCTR Endocrine Disruptor Knowledge Base
Main Citation: Fang, H., W. Tong, L.M. Shi, R. Blair, R. Perkins, W. Branham, B.S. Hass, Q. Xie, S.L. Dial, C.L. Moland, and D.M. Sheehan (2001) Structure-activity relationships for a large diverse set of natural, synthetic, and environmental estrogens. Chem. Res. Tox., 14:280-294.
Data Table (Concise)