## Endpoint to Predict
- Endpoint scope: assay
- Measurement type: IC50
- Label type: continuous
- Binary semantics: pchembl
- Assay description: Electrophysiological Assay (EP) (In vitro Assay): Patch voltage clamp electrophysiology allows for the direct measurement and quantification of block of voltage-gated sodium channels (NaV's), and allows the determination of the time- and voltage-dependence of block which has been interpreted as differential binding to the resting, open, and inactivated states of the sodium channel (Hille, B., Journal of General Physiology (1977), 69: 497-515).The following patch voltage clamp electrophysiology studies were performed on representative compounds of the invention using human embryonic kidney cells (HEK), permanently transfected with an expression vector containing the full-length cDNA coding for the desired human sodium channel α-subunit, grown in culture media containing 10% FBS, 1% PSG, and 0.5 mg/mL G418 at 37° C. with 5% CO2. HEK cells used for the electrophysiology (EP) recordings had a passage number of less than 40 for all studies and were used within three days from the time of plating, NaV1.7 and NaV1.5 cDNAs (NM_002977 and AC137587; SCN5A, respectively) were stably expressed in HEK-293 cells. The β1 subunit was coexpressed in both the NaV1.7 and NaV1.5 cell lines.Sodium currents were measured rising the patch clamp technique in the whole-cell configuration using either a PatchXpress automated voltage clamp or manually using an Axopatch 200B (Axon Instruments) or Model 2400 (A-M systems) amplifier. The manual voltage clamp protocol was as follows: Borosilicate glass micropipettes were fire-polished to a tip diameter yielding a resistance of 2-4 Mohms in the working solutions. The pipette was filled with a solution comprised of: 5 mM NaCl, 10 mM CsCl, 120 mM CsF, 0.1 mM CaCl2, 2 mM MgCl2, 10 mM HEPES, 10 mM EGTA; and adjusted to pH 7.2 with CsOH. The external solution had the following composition: 140 mM NaCl, 5 mM KCl, 2 mM CaCl2, 1 mM MgCl2, 10 mM HEPES; and adjusted to pH 7.4 with NaOH. In some studies, the external sodium was reduced by equimolar replacement with choline. Osmolality in the CsF internal and NaCl external solutions was adjusted to 300 mOsm/kg and 310 mOsm/kg with glucose, respectively. All recordings were performed at ambient temperature in a bath chamber with a volume of 150 μL. Control sodium currents were measured in 0.5% DMSO.
- Target name: Unchecked
- Target type: UNCHECKED

## Reference Molecule A
- Canonical SMILES: O=C(NS(=O)(=O)N1CCC1)c1cc(C2CC2)c(OCC2CC3CCC(C2)N3C(c2ccccc2)c2ccccc2)cc1F
- Properties:
- ChEMBL ID: CHEMBL5992687
- Molecular weight: 603.76
- Heavy atoms: 43
- Hydrogen bond donors: 1
- Hydrogen bond acceptors: 5
- TPSA: 78.95
- LogP: 5.79
- Rotatable bonds: 10
- Ring count: 7
- Aromatic rings: 3
- Formal charge: 0
- Fraction Csp3: 0.44
- QED: 0.32

## Known Reference Result on This Endpoint
- Molecule A clean result: median pChEMBL = 6.7
- This result is provided as context for predicting Molecule B on the same endpoint.

## Reference Molecule A Other ChEMBL Evidence
- type IC50; relation =; value 199; units nM; pChEMBL 6.7; comment 498852

## Query Molecule B
- Canonical SMILES: COC[C@H](c1cc(Cl)cc(Cl)c1)N1CCC(COc2cc(F)c(C(=O)NS(=O)(=O)C3CC3)cc2C2CC2)CC1
- Properties:
- ChEMBL ID: CHEMBL5820839
- Molecular weight: 599.55
- Heavy atoms: 39
- Hydrogen bond donors: 1
- Hydrogen bond acceptors: 6
- TPSA: 84.94
- LogP: 5.71
- Rotatable bonds: 11
- Ring count: 5
- Aromatic rings: 2
- Formal charge: 0
- Fraction Csp3: 0.54
- QED: 0.36

## Molecule Similarity
- Weighted Tanimoto: 0.5

Answer: 7.31