## Endpoint to Predict
- Endpoint scope: assay
- Measurement type: IC50
- Label type: continuous
- Binary semantics: pchembl
- Assay description: In Vitro Measure of Sodium Channel Blocking Activity and Reversibility: One assay used to assess mechanism of action and/or potency of the compounds of the present invention involves the determination of lumenal drug inhibition of airway epithelial sodium currents measured under short circuit current (ISC) using airway epithelial monolayers mounted in Using chambers. This assay is described in detail in Hirsh, A. J., Zhang, J., Zamurs, A., et al. Pharmacological properties of N-(3,5-diamino-6-chloropyrazine-2-carbonyl)-N′-4-[4-(2,3-dihydroxypropoxy)phenyl]butyl-guanidine methanesulfonate (552-02), a novel epithelial sodium channel blocker with potential clinical efficacy for CF lung disease. J. Pharmacol. Exp. Ther. 2008; 325(1): 77-88. Cells obtained from freshly excised human, dog, sheep or rodent airways are seeded onto porous 0.4 micron Snapwell Inserts (CoStar), cultured at air-liquid interface (ALI) conditions in hormonally defined media, and assayed for sodium transport activity (ISC) while bathed in Krebs Bicarbonate Ringer (KBR) in Using chambers. All test drug additions are to the lumenal bath with half-log dose addition protocols (from 1×10−11 M to 3×10−5 M), and the cumulative change in ISC (inhibition) recorded. All drugs are prepared in dimethyl sulfoxide as stock solutions at a concentration of 1×10−2 M and stored at −20° C. Eight preparations are typically run in parallel; two preparations per run incorporate amiloride and/or benzamil as positive controls. After the maximal concentration (5×10−5 M) is administered, the lumenal bath is exchanged three times with fresh drug-free KBR solution, and the resultant ISC measured after each wash for approximately 5 minutes in duration. Reversibility is defined as the percent return to the baseline value for sodium current after the third wash. All data from the voltage clamps are collected via a computer interface and analyzed off-line.Dose-effect relationships for all compounds are considered and analyzed by the Prism 3 program. IC50 values, maximal effective concentrations, and reversibility are calculated and compared to amiloride and benzamil as positive controls.
- Target name: Unchecked
- Target type: UNCHECKED

## Reference Molecule A
- Canonical SMILES: N=C(NCCCCc1ccc2cc(C[C@H](NCCCN(C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO)C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO)C(N)=O)ccc2c1)NC(=O)c1nc(Cl)c(N)nc1N
- Properties:
- ChEMBL ID: CHEMBL6060425
- Molecular weight: 883.4
- Heavy atoms: 61
- Hydrogen bond donors: 17
- Hydrogen bond acceptors: 19
- TPSA: 403.46
- LogP: -4.73
- Rotatable bonds: 26
- Ring count: 3
- Aromatic rings: 3
- Formal charge: 0
- Fraction Csp3: 0.55
- QED: 0.02

## Known Reference Result on This Endpoint
- Molecule A clean result: median pChEMBL = 7.56
- This result is provided as context for predicting Molecule B on the same endpoint.

## Reference Molecule A Other ChEMBL Evidence
- type IC50; relation =; value 27.4; units nM; pChEMBL 7.56; comment 739015

## Query Molecule B
- Canonical SMILES: CCCCCCN(CCCN[C@@H](CCc1ccc(CCCCNC(=N)NC(=O)c2nc(Cl)c(N)nc2N)cc1)C(N)=O)C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
- Properties:
- ChEMBL ID: CHEMBL5805497
- Molecular weight: 767.37
- Heavy atoms: 53
- Hydrogen bond donors: 12
- Hydrogen bond acceptors: 14
- TPSA: 302.31
- LogP: -0.34
- Rotatable bonds: 26
- Ring count: 2
- Aromatic rings: 2
- Formal charge: 0
- Fraction Csp3: 0.63
- QED: 0.03

## Molecule Similarity
- Weighted Tanimoto: 0.76

Answer: 8.59