## Endpoint to Predict
- Endpoint scope: assay
- Measurement type: IC50
- Label type: continuous
- Binary semantics: pchembl
- Assay description: Electrophysiology Assay: Block of Kir1.1 (ROMK1) currents was examined by whole cell voltage clamp (Hamill et. al. Pfluegers Archives 391:85-100 (1981)) using the IonWorks Quattro automated electrophysiology platform (Molecular Devices, Sunnyvale, Calif.). Chinese hamster ovary cells stably expressing Kir1.1 channels were maintained in T-75 flasks in cell culture media in a humidified 10% CO2 incubator at 37° C. Prior to an experiment, Kir1.1 expression was induced by overnight incubation with 1 mM sodium butyrate. On the day of the experiment, cells were dissociated with 2.5 mL of Versene (Invitrogen 15040-066) for approximately 6 min at 37° C. and suspended in 10 mL of bath solution containing (in mM): 150 NaCl, 10 KCl, 2.7 CaCl2, 0.5 MgCl2, 5 HEPES, pH 7.4. After centrifugation, the cell pellet was resuspended in approximately 4 mL of bath solution and placed in the IonWorks instrument. The intracellular solution consisted of (in mM): 80 K gluconate, 40 KCl, 20 KF, 3.2 MgCl2, 3 EGTA, 5 Hepes, pH 7.4. Electrical access to the cytoplasm was achieved by perforation in 0.13 mg/mL amphotericin B for 4 min. Amphotericin B (Sigma A-4888) was prepared as a 40 mg/mL solution in DMSO. Voltage protocols and current recordings were performed using the IonWorks HT software/hardware system. Currents were sampled at 1 kHz. No correction for liquid junction potentials was used. The test pulse, consisting of a 100 ms step to 0 mV from a holding potential of −70 mV, followed by a 100 ms voltage ramp from −70 mV to +70 mV, was applied before and after a 6 min compound incubation period. Test compounds were prepared by diluting DMSO stock solutions into the bath solution at 3× the final concentration and placed in the instrument in 96-well polypropylene plates.
- Assay organism: Homo sapiens
- Target name: ATP-sensitive inward rectifier potassium channel 1
- Target type: SINGLE PROTEIN
- Target organism: Homo sapiens

## Reference Molecule A
- Canonical SMILES: Cc1cc2c(cc1C(O)CN1CCN3C[C@@H](c4ccc5c(c4C)COC5=O)OC[C@@H]3C1)COC2=O
- Properties:
- ChEMBL ID: CHEMBL5831129
- Molecular weight: 478.55
- Heavy atoms: 35
- Hydrogen bond donors: 1
- Hydrogen bond acceptors: 8
- TPSA: 88.54
- LogP: 2.44
- Rotatable bonds: 4
- Ring count: 6
- Aromatic rings: 2
- Formal charge: 0
- Fraction Csp3: 0.48
- QED: 0.67

## Known Reference Result on This Endpoint
- Molecule A clean result: median pChEMBL = 6.99
- This result is provided as context for predicting Molecule B on the same endpoint.

## Reference Molecule A Other ChEMBL Evidence
- type IC50; relation =; value 80; units nM; pChEMBL 7.1; comment 603279
- type IC50; relation =; value 130; units nM; pChEMBL 6.89; comment 603280

## Query Molecule B
- Canonical SMILES: CCOc1cc(CCN2CCN3C[C@@H](c4ccc5c(c4C)COC5=O)OC[C@@H]3C2)ccc1C#N
- Properties:
- ChEMBL ID: CHEMBL5835665
- Molecular weight: 461.56
- Heavy atoms: 34
- Hydrogen bond donors: 0
- Hydrogen bond acceptors: 7
- TPSA: 75.03
- LogP: 3.24
- Rotatable bonds: 6
- Ring count: 5
- Aromatic rings: 2
- Formal charge: 0
- Fraction Csp3: 0.48
- QED: 0.61

## Molecule Similarity
- Weighted Tanimoto: 0.55

Answer: 7.05