## Endpoint to Predict
- Endpoint scope: assay
- Measurement type: IC50
- Label type: continuous
- Binary semantics: pchembl
- Assay description: MK-499 Filter Binding Assay: Drug cardiac arrhythmia is an important safety concern for pharmaceutical development and health regulatory authorities. Blockade of heterologously-expressed human ether-a-go-go gene (hERG) channel prolongs the duration of the cardiac action potential leading to a long QT interval that can lead to sudden death (De Ponti, F.; et al Drug Safety 2002, 25, pp. 263-286). It is important to have compounds devoid of hERG channel activity as measured by an in vitro assay. Affinity of compounds for the hERG channel was evaluated in radioligand competition experiments using HEK293 cells that were stably transfected with the hERG channel and radiolabeled ligand, MK-499 a potent antiarrhythmic. This assay correlates well with QT prolongation in vivo (Jamieson, C.; et al., J. Med. Chem. 2006, 49, pp. 5029-5046). 25 μL Target membranes (in assay buffer: 10 mM HEPES/NaOH, pH 7.4, 70 mM NaCl, 60 mM KCl, 2 mM MgCl2, 1 mM CaCl2) purified from a HEK293 cell line expressing the human Ether-á-go-go Related Gene (hERG) ion channel, 1 μL test compound in 10 mM DMSO and 25 μL (6,000 cpm/well; in assay buffer) [35S]MK-0499 radioligand (Merck/Perkin Elmer) were added to the assay plate (Axygen; 384 Deep well ¿Diamond Plate¿, clear). After incubation of the binding reaction at room temperature (RT) for 90 min 50 μL of the assay were transferred to a Multiscreen HTS 384 FC filter plate (Millipore), which had been pre-wetted with 20 μL 0.01% PEI/0.01% Triton X-100 for at least 30 min at RT. Then, 30 μL wash buffer (10 mM HEPES/NaOH, pH 7.4, 130 mM NaCl, 2 mM MgCl2, 1 mM CaCl2) equilibrated to RT were added to each well of the assay plate and subsequently transferred to the filter plate. The assay mixture was aspirated through the filter plate using a Biotek ELx405¿ washer. The filter plate was washed twice with 100 μl cold wash buffer per wash and well and then dried in a drying oven for at least 75 min at 55° C. Afterwards, the bottom of each filter plate was heat sealed with a solid foil seal, then 10 μL of Microscint¿ 0 (Perkin Elmer) were added to each well of the filter plate and finally, the top of each filter plate was sealed with a clear seal. The plates were stored for at least 20 min in a MicroBeta2 reader (Perkin Elmer) before they are counted (60 sec/well).
- Assay organism: Homo sapiens
- Target name: Voltage-gated inwardly rectifying potassium channel KCNH2
- Target type: SINGLE PROTEIN
- Target organism: Homo sapiens

## Reference Molecule A
- Canonical SMILES: C[C@H]1OC(=O)[C@]2(CC(N)=O)CC(F)(F)[C@@H](C)[C@H](/C=C/c3ccc(-c4cccc(F)c4)cn3)[C@H]12
- Properties:
- ChEMBL ID: CHEMBL5741564
- Molecular weight: 458.48
- Heavy atoms: 33
- Hydrogen bond donors: 1
- Hydrogen bond acceptors: 4
- TPSA: 82.28
- LogP: 4.62
- Rotatable bonds: 5
- Ring count: 4
- Aromatic rings: 2
- Formal charge: 0
- Fraction Csp3: 0.4
- QED: 0.66

## Known Reference Result on This Endpoint
- Molecule A clean result: median pChEMBL = 4.69
- This result is provided as context for predicting Molecule B on the same endpoint.

## Reference Molecule A Other ChEMBL Evidence
- type IC50; relation =; value 20400; units nM; pChEMBL 4.69; comment 492330

## Query Molecule B
- Canonical SMILES: C[C@H]1OC(=O)[C@]2(C(N)=O)CC(F)(F)[C@@H](C)[C@H](/C=C/c3ccc(-c4cccc5c4OC(F)(F)O5)cn3)[C@H]12
- Properties:
- ChEMBL ID: CHEMBL5758218
- Molecular weight: 506.45
- Heavy atoms: 36
- Hydrogen bond donors: 1
- Hydrogen bond acceptors: 6
- TPSA: 100.74
- LogP: 4.41
- Rotatable bonds: 4
- Ring count: 5
- Aromatic rings: 2
- Formal charge: 0
- Fraction Csp3: 0.4
- QED: 0.37

## Molecule Similarity
- Weighted Tanimoto: 0.58

Answer: 4.81