## Endpoint to Predict
- Endpoint scope: assay
- Measurement type: EC50
- Label type: continuous
- Binary semantics: pchembl
- Assay description: Intracellular Ca2+ Mobilization Assay: A monoclonal HEK-293 cell line stably transfected with a cDNA encoding for the human mGlu5a receptor was generated; for the work with mGlu5 Positive Allosteric Modulators (PAMs), a cell line with low receptor expression levels and low constitutive receptor activity was selected to allow the differentiation of agonistic versus PAM activity. Cells were cultured according to standard protocols (Freshney, 2000) in Dulbecco's Modified Eagle Medium with high glucose supplemented with 1 mM glutamine, 10% (vol/vol) heat-inactivated bovine calf serum, Penicillin/Streptomycin, 50 μg/ml hygromycin and 15 μg/ml blasticidin (all cell culture reagents and antibiotics from Invitrogen, Basel, Switzerland). bout 24 hrs before an experiment, 5×104 cells/well were seeded in poly-D-lysine coated, black/clear-bottomed 96-well plates. The cells were loaded with 2.5 μM Fluo-4AM in loading buffer (1×HBSS, 20 mM HEPES) for 1 hr at 37 °C. and washed five times with loading buffer. The cells were transferred into a Functional Drug Screening System 7000 (Hamamatsu, Paris, France), and 11 half logarithmic serial dilutions of test compound at 37 °C. were added and the cells were incubated for 10-30 min. with on-line recording of fluorescence. Following this pre-incubation step, the agonist L-glutamate was added to the cells at a concentration corresponding to EC20 (typically around 80 μM) with on-line recording of fluorescence; in order to account for day-to-day variations in the responsiveness of cells, the EC20 of glutamate was determined immediately ahead of each experiment by recording of a full dose-response curve of glutamate. Responses were measured as peak increase in fluorescence minus basal (i.e. fluorescence without addition of L-glutamate), normalized to the maximal stimulatory effect obtained with saturating concentrations of L-glutamate.
- Assay cell type: HEK293
- Target name: Metabotropic glutamate receptor 5
- Target type: SINGLE PROTEIN
- Target organism: Homo sapiens

## Reference Molecule A
- Canonical SMILES: O=C1OC2(CCCC2)CN1c1ccc(C#Cc2ccccc2)cn1
- Properties:
- ChEMBL ID: CHEMBL3978273
- Molecule type: Small molecule
- Molecular weight: 318.38
- Heavy atoms: 24
- Hydrogen bond donors: 0
- Hydrogen bond acceptors: 3
- TPSA: 42.43
- LogP: 3.75
- Rotatable bonds: 1
- Ring count: 4
- Aromatic rings: 2
- Formal charge: 0
- Fraction Csp3: 0.3
- QED: 0.75

## Known Reference Result on This Endpoint
- Molecule A clean result: median pChEMBL = 7.41
- This result is provided as context for predicting Molecule B on the same endpoint.

## Reference Molecule A Other ChEMBL Evidence
- type EC50; relation =; value 39; units nM; pChEMBL 7.41; comment 389491

## Query Molecule B
- Canonical SMILES: CC1(C)CCN(c2ccc(C#Cc3ccc(F)cc3)cn2)C(=O)C1
- Properties:
- ChEMBL ID: CHEMBL3941237
- Molecule type: Small molecule
- Molecular weight: 322.38
- Heavy atoms: 24
- Hydrogen bond donors: 0
- Hydrogen bond acceptors: 2
- TPSA: 33.2
- LogP: 3.77
- Rotatable bonds: 1
- Ring count: 3
- Aromatic rings: 2
- Formal charge: 0
- Fraction Csp3: 0.3
- QED: 0.75

## Molecule Similarity
- Weighted Tanimoto: 0.43

Answer: 7.17