## Endpoint to Predict
- Endpoint scope: assay
- Measurement type: Ki
- Label type: continuous
- Binary semantics: pchembl
- Assay description: Receptor Radioligand Binding Assay: Human Embryonic Kidney 293 cells (HEK293) stably expressing rat orexin 1 receptor (Genebank accession number NM_001525) or Chinese ovary cells (CHO) stably expressing human orexin 1 receptor (Genebank accession number NM_001526) were grown to confluency in DMEM (Hyclone, cat # SH30022), 10% FBS, 1× Pen/Strep, 1× sodium pyruvate, 10 mM HEPES, 600 μg/mL G418 and DMEM/F12 (Gibco, Cat #11039), 10% FBS, 1× Pen/Strep, 600 μg/mL G418 media, respectively on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1× with Calcium and Magnesium, Cat # SH3264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2K×G, 5 min at 4° C.), the supernatant was aspirated and the pellets frozen and stored at −80° C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL. Each cell pellet from a 15 cm plate was resuspended in 10 mL, stored on ice, and homogenized for 45 sec prior to addition to the reactions. Competition binding experiments in 96 well polypropylene plates were performed using [3H] (1-(5-(2-fluoro-phenyl)-2-methyl-thiazol-4-yl)-1-((S)-2-(5-phenyl-(1,3,4)oxadiazol-2-ylmethyl)-pyrrolidin-1-yl)-methanone) (Moraveck Corporation, specific activity=35.3 Ci/mmol), diluted to a 10 nM concentration in PBS (4 nM final). Compounds were solubilized in 100% DMSO (Acros Organics, Cat. #61042-1000) and tested over a range of 7 concentrations (from 0.1 nM to 10 μM). The final concentration of DMSO in the reactions is equal to or less than 0.1%. Total and nonspecific binding was determined in the absence and presence of 10 μM almorexant. The total volume of each reaction is 200 μL (20 μL of diluted compounds, 80 μL of [3H]¿ (1-(5-(2-fluoro-phenyl)-2-methyl-thiazol-4-yl)-1-((S)-2-(5-phenyl-(1,3,4)oxadiazol-2-ylmethyl)-pyrrolidin-1-yl)-methanone) diluted in PBS and 100 μL of the cell suspension). Reactions were run for 60 min at room temperature and terminated by filtration through GF/C filter plates (PerkinElmer, Cat. #6005174) presoaked in 0.3% polyethylenimine using the cell harvester (PerkinElmer Filtermate).
- Assay organism: Homo sapiens
- Target name: Unchecked
- Target type: UNCHECKED

## Reference Molecule A
- Canonical SMILES: Cc1ccc(-n2nccn2)c(C(=O)N2C(C)C3CC(Oc4ccc(C(F)(F)F)cn4)C2C3)n1
- Properties:
- ChEMBL ID: CHEMBL5803148
- Molecular weight: 458.44
- Heavy atoms: 33
- Hydrogen bond donors: 0
- Hydrogen bond acceptors: 6
- TPSA: 86.03
- LogP: 3.46
- Rotatable bonds: 4
- Ring count: 5
- Aromatic rings: 3
- Formal charge: 0
- Fraction Csp3: 0.41
- QED: 0.6

## Known Reference Result on This Endpoint
- Molecule A clean result: median pChEMBL = 6.22
- This result is provided as context for predicting Molecule B on the same endpoint.

## Reference Molecule A Other ChEMBL Evidence
- type Ki; relation =; value 649; units nM; pChEMBL 6.19; comment 609415
- type Ki; relation =; value 426; units nM; pChEMBL 6.37; comment 609418
- type Ki; relation =; value 861; units nM; pChEMBL 6.07; comment 609520
- 3 additional provenance rows omitted

## Query Molecule B
- Canonical SMILES: CC1C2CC(Oc3ccc(C(F)(F)F)cn3)C(C2)N1C(=O)c1ccccc1-c1cccc(Br)n1
- Properties:
- ChEMBL ID: CHEMBL5982522
- Molecular weight: 532.36
- Heavy atoms: 34
- Hydrogen bond donors: 0
- Hydrogen bond acceptors: 4
- TPSA: 55.32
- LogP: 6
- Rotatable bonds: 4
- Ring count: 5
- Aromatic rings: 3
- Formal charge: 0
- Fraction Csp3: 0.32
- QED: 0.39

## Molecule Similarity
- Weighted Tanimoto: 0.56

Answer: 6.08