## Endpoint to Predict
- Endpoint scope: assay
- Measurement type: IC50
- Label type: continuous
- Binary semantics: pchembl
- Assay description: Steroid Inhibition of TBPS Binding: TBPS binding assays using rat brain cortical membranes in the presence of 5 μM GABA has been described (Gee et al, J. Pharmacol. Exp. Ther. 1987, 241, 346-353; Hawkinson et al, Mol. Pharmacol. 1994, 46, 977-985; Lewin, A. H et al., Mol. Pharmacol. 1989, 35, 189-194).Briefly, cortices are rapidly removed following decapitation of carbon dioxide-anesthetized Sprague-Dawley rats (200-250 g). The cortices are homogenized in 10 volumes of ice-cold 0.32 M sucrose using a glass/teflon homogenizer and centrifuged at 1500×g for 10 min at 4° C. The resultant supernatants are centrifuged at 10,000×g for 20 min at 4° C. to obtain the P2 pellets. The P2 pellets are resuspended in 200 mM NaCl/50 mM NaK phosphate pH 7.4 buffer and centrifuged at 10,000×g for 10 min at 4° C. This washing procedure is repeated twice and the pellets are resuspended in 10 volumes of buffer. Aliquots (100 μL) of the membrane suspensions are incubated with 3 nM [35S]-TBPS and 5 μL aliquots of test drug dissolved in dimethyl sulfoxide (DMSO) (final 0.5%) in the presence of 5 μM GABA. The incubation is brought to a final volume of 1 mL with buffer. Nonspecific binding is determined in the presence of 2 μM unlabeled TBPS and ranged from 15 to 25%. Following a 90 min incubation at room temp, the assays are terminated by filtration through glass fiber filters (Schleicher and Schuell No. 32) using a cell harvester (Brandel) and rinsed three times with ice-cold buffer. Filter bound radioactivity is measured by liquid scintillation spectrometry. Non-linear curve fitting of the overall data for each drug averaged for each concentration is done using Prism (GraphPad). The data are fit to a partial instead of a full inhibition model if the sum of squares is significantly lower by F-test. Similarly, the data are fit to a two component instead of a one component inhibition model if the sum of squares is significantly lower by F-test. The concentration of test compound producing 50% inhibition (IC50) of specific binding and the maximal extent of inhibition (Imax) are determined for the individual experiments with the same model used for the overall data and then the means±SEM.s of the individual experiments are calculated. Picrotoxin serves as the positive control for these studies as it has been demonstrated to robustly inhibit TBPS binding.Various compounds are or can be screened to determine their potential as modulators of [35S]-TBPS binding in vitro. These assays are or can be performed in accordance with the above discussed procedures.
- Assay organism: Rattus norvegicus
- Target name: Gamma-aminobutyric acid type B receptor subunit 1
- Target type: SINGLE PROTEIN
- Target organism: Rattus norvegicus

## Reference Molecule A
- Canonical SMILES: COC[C@]12CC[C@@](C)(O)C[C@@H]1CC[C@H]1[C@@H]3CC[C@H](C(=O)Cn4ncc5ccc(OC)cc54)[C@@]3(C)CC[C@@H]12
- Properties:
- ChEMBL ID: CHEMBL5833840
- Molecular weight: 508.7
- Heavy atoms: 37
- Hydrogen bond donors: 1
- Hydrogen bond acceptors: 5
- TPSA: 73.58
- LogP: 5.65
- Rotatable bonds: 6
- Ring count: 6
- Aromatic rings: 2
- Formal charge: 0
- Fraction Csp3: 0.74
- QED: 0.55

## Known Reference Result on This Endpoint
- Molecule A clean result: median pChEMBL = 7.12
- This result is provided as context for predicting Molecule B on the same endpoint.

## Reference Molecule A Other ChEMBL Evidence
- type IC50; relation =; value 75; units nM; pChEMBL 7.12; comment 1095400

## Query Molecule B
- Canonical SMILES: COC[C@]12CC[C@@](C)(O)C[C@H]1CC[C@H]1[C@@H]3CC[C@H](C(=O)Cn4cc([S+](C)[O-])cn4)[C@@]3(C)CC[C@@H]12
- Properties:
- ChEMBL ID: CHEMBL5960322
- Molecular weight: 490.71
- Heavy atoms: 34
- Hydrogen bond donors: 1
- Hydrogen bond acceptors: 5
- TPSA: 87.41
- LogP: 4.23
- Rotatable bonds: 6
- Ring count: 5
- Aromatic rings: 1
- Formal charge: 0
- Fraction Csp3: 0.85
- QED: 0.6

## Molecule Similarity
- Weighted Tanimoto: 0.62

Answer: 6.52