## Endpoint to Predict
- Endpoint scope: assay
- Measurement type: IC50
- Label type: continuous
- Binary semantics: pchembl
- Assay description: Ca Flux Activity Assay: The 5-HT3 antagonist activity of the compounds of the invention was determined by measuring the ability of the compounds to inhibit the calcium flux activity of 3HT3a receptor expressed in HEK-293T cells. HEK-293T cells were transfected with the 5-HT3a expression construct using Xtreme Gene 9 (Roche) in 150 mm tissue culture treated plates and incubated for 24 hours at 37° C. Cells were then split and plated at a density of 60K cells/well in poly-lysine coated, black 96-well plates with clear bottoms (BD BioSciences) and incubated overnight at 37° C. Growth media was removed and cells loaded with 200 μL calcium indicator dye in HBSS containing 20 mM HEPES (Calcium 5 Assay kit, Molecular Devices) and incubated at 37° C. for 1 hour. While cells were incubating, the 10× antagonist and agonist/antagonist addition plates were made. For 10× antagonist plate: half log serial dilutions (final concentrations range from 10^−7 through 10^−10 with the bottom well a negative, no ligand control) were made from test compounds in DMSO at a 1000× concentration and then diluted to 10× in HBSS/20 mM HEPES. For addition plate: 5HT was diluted to 100× in HBSS/20 mM HEPES (final concentration in the assay−216 nM) and 15 μL was added to each well of the addition plate, 15 μL of 10× compound was also added to the addition plate, and finally 120 μL of HBSS/20 mM HEPES (for a total of 150 μL). Cells were then removed from the incubator and equilibrated to room temperature for 10 minutes, then 22.5 μL of 10× test compounds were added in triplicate to the plates and incubated at room temperature for 10 minutes (Tropisetron was used as a positive control in every assay). Test plate and addition plate were loaded into the FlexStation III (Molecular Devices), and using the fluidics, 22.5 μL compound additions were made (at t=~17 seconds), and fluorescence was measured for 90 seconds, reading every 2.2 seconds.
- Assay organism: Homo sapiens
- Assay cell type: HEK-293T
- Target name: 5-hydroxytryptamine receptor 3A
- Target type: SINGLE PROTEIN
- Target organism: Homo sapiens

## Reference Molecule A
- Canonical SMILES: CN1[C@@H]2COC[C@H]1C[C@@H](NC(=O)c1cn(-c3ccnn3C)c3ccccc13)C2
- Properties:
- ChEMBL ID: CHEMBL3979768
- Molecule type: Small molecule
- Molecular weight: 379.46
- Heavy atoms: 28
- Hydrogen bond donors: 1
- Hydrogen bond acceptors: 4
- TPSA: 64.32
- LogP: 1.96
- Rotatable bonds: 3
- Ring count: 5
- Aromatic rings: 3
- Formal charge: 0
- Fraction Csp3: 0.43
- QED: 0.76

## Known Reference Result on This Endpoint
- Molecule A clean result: median pChEMBL = 9
- This result is provided as context for predicting Molecule B on the same endpoint.

## Reference Molecule A Other ChEMBL Evidence
- type IC50; relation =; value 1.01; units nM; pChEMBL 9; comment 407236

## Query Molecule B
- Canonical SMILES: N#Cc1cc(-n2cc(C(=O)O[C@H]3C[C@H]4COC[C@@H](C3)N4)c3ccccc32)ccn1
- Properties:
- ChEMBL ID: CHEMBL3966403
- Molecule type: Small molecule
- Molecular weight: 388.43
- Heavy atoms: 29
- Hydrogen bond donors: 1
- Hydrogen bond acceptors: 6
- TPSA: 89.17
- LogP: 2.57
- Rotatable bonds: 3
- Ring count: 5
- Aromatic rings: 3
- Formal charge: 0
- Fraction Csp3: 0.32
- QED: 0.69

## Molecule Similarity
- Weighted Tanimoto: 0.33

Answer: 8.43