## Endpoint to Predict
- Endpoint scope: assay
- Measurement type: Ki
- Label type: continuous
- Binary semantics: pchembl
- Assay description: 3H]-Spiperone Binding Assay: CHO cells stably expressing human dopamine receptor type 2, long variant (hD2L), coupled to Gα16 protein (CHO-Gα16-hD2L) were re-suspended in 20 mM HEPES, 2 mM EDTA (pH 7.4), homogenised and centrifuged at 40,000 g (20 min, 4° C.). After re-suspension, homogenization and centrifugation as above, the final pellet was re-suspended in 20 mM HEPES, 100 mM NaCl, 10 mM MgCl2, 1 mM EDTA (pH 7.4) and aliquots were kept at −80° C. [3H]-Spiperone Binding experiments were performed in 96 deep-well polypropylene plates in 50 mM Tris/HCl, 120 mM NaCl, 5 mM KCl, 5 mM MgCl2 (pH 7.4). Compounds of invention were serially diluted in DMSO at 100 fold final concentrations in the assay (1% DMSO final in the assay). Displacement was performed in the presence of 0.08 nM [3H]-Spiperone. The reaction was initiated by the addition of membrane suspension (2 μg of protein for CHO-hD2 membranes) and lasted for 120 min at 23° C. in a final volume of 1000 μl. Non specific binding (NSB) was determined in the presence of 0.1 μM Spiperone. The binding reaction was stopped by rapid filtration through GF/B filterplates pre-soaked in 0.5% polyetylenimmine (PEI) using a Packard cell harvester. After washing with ice-cold 0.9% NaCl, the plate was left to dry before the addition of Microscint 20 (50 μl/well, PerkinElmer). Radioactivity was counted with a TopCount (PerkinElmer). Data were analysed by non-linear regression analysis using GraphPad Prism 5 (GraphPad Software) or XLfit Version 5.2.0 (Copyright © 2006-2009 ID Business Solutions Ltd). Saturation binding experiments were performed similar to the competition binding experiments using a radioligand concentrations ranging from 0.01 to 3 nM. Ref: Durcan M. J. et al. (1995). Is Clozapine selective for the dopamine D4 receptor? Life Sciences, 57: 275-283. Petrus J. et al. (2001).
- Target name: Unchecked
- Target type: UNCHECKED

## Reference Molecule A
- Canonical SMILES: Cn1cc(-c2nnc(SCCCN3CC[C@]4(CC4c4ccc(C(F)(F)F)cc4)C3)n2C)cn1
- Properties:
- ChEMBL ID: CHEMBL5818912
- Molecular weight: 476.57
- Heavy atoms: 33
- Hydrogen bond donors: 0
- Hydrogen bond acceptors: 5
- TPSA: 51.77
- LogP: 4.6
- Rotatable bonds: 7
- Ring count: 5
- Aromatic rings: 3
- Formal charge: 0
- Fraction Csp3: 0.52
- QED: 0.37

## Known Reference Result on This Endpoint
- Molecule A clean result: median pChEMBL = 6.2
- This result is provided as context for predicting Molecule B on the same endpoint.

## Reference Molecule A Other ChEMBL Evidence
- type Ki; relation =; value 759; units nM; pChEMBL 6.12; comment 735068
- type Ki; relation =; value 537; units nM; pChEMBL 6.27; comment 735071

## Query Molecule B
- Canonical SMILES: CC(=O)N1CC(c2nnc(SCCCN3CC[C@]4(C[C@@H]4c4ccc(C(F)(F)F)cc4)C3)n2C)C1
- Properties:
- ChEMBL ID: CHEMBL5821451
- Molecular weight: 493.6
- Heavy atoms: 34
- Hydrogen bond donors: 0
- Hydrogen bond acceptors: 5
- TPSA: 54.26
- LogP: 4.14
- Rotatable bonds: 7
- Ring count: 5
- Aromatic rings: 2
- Formal charge: 0
- Fraction Csp3: 0.62
- QED: 0.43

## Molecule Similarity
- Weighted Tanimoto: 0.63

Answer: 5.56