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BioAssay: AID 1204

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 ..
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 Tested Compounds
 Tested Compounds
All(232)
 
 
Active(131)
 
 
Inactive(93)
 
 
Inconclusive(8)
 
 
 Tested Substances
 Tested Substances
All(232)
 
 
Active(131)
 
 
Inactive(93)
 
 
Inconclusive(8)
 
 
 Related BioAssays
 Related BioAssays
AID: 1204
Data Source: EPA DSSTox (DSSTox_AID10)
BioAssay Type: Primary, Primary Screening, Single Concentration Activity Observed
BioAssay Version:
Deposit Date: 2008-03-05
Modify Date: 2008-03-12

Data Table ( Complete ):           View Active Data    View All Data
BioActive Compounds: 131
Description:
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.
Protocol
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
Comment
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.
Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
ScoreThe BioAssay activity ranking scoreInteger
1ER_RBAEstrogen receptor relative binding affinity determined using a competitive receptor binding assay in which a chemical competes with radiolabeled estradiol (E2) for binding to the ER in rat uterine cytosol and the IC50 is measured. 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).Float
2ActivityCategory_ER_RBAFor purposes of SAR analysis, NCTRER Main Citation (Fang et al., 2001) divided the NCTRER data set into five main activity categories: active strong (ER_RBA > 1); active medium (1> ER_RBA > 0.01); active weak (0.01 > ER_RBA > 1E-5); slight binder (max< 50% inhibition or ER_RBA< 1E-5); inactive (no activity, equates with NA designation). String
3ChemClass_ERBSix main estrogenic receptor binding (ERB) structural classes with subclass designations utilized in the NCTRER Main Citation (Fang et al., 2001). #Misc# (Miscellaneous) category contains structurally diverse compounds that do not fit into one of the six main structural classes. Main structural class (e.g., Phytoestrogens) is listed before subclass, as in, e.g., Phytoestrogens Flavones or Biphenyls PCBs.String
4ActivityCategory_Rationale_ChemClass_ERBQualitative structure-activity rationale relating what is known or inferred concerning the structural basis for estrogenic activity within each of the 20 structural subclasses (ChemClass_ERB). Brief narrative statement intended to summarize the lengthier discussion in the NCTRER Main Citation (Fang et al., 2001).String

Data Table (Concise)
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