## Endpoint to Predict
- Endpoint scope: assay
- Measurement type: IC50
- Label type: continuous
- Binary semantics: pchembl
- Assay description: CYP P450 Enzyme Inhibition: Inhibitory activities of test compounds on 5 major isoforms of CYP P450 were evaluated by using pooled human liver microsome (HLM, purchased from BD Gentest) and selective substrates for those isoforms. Those CYP isoforms and their corresponding probe substrates are as follows: CYP1A2 (phenacetin, 30 μM), CYP2C9 (tolutamide, 100 μM), CYP2C19 (S-mephenytoin, 40 μM), CYP2D6 (dextromethorphan, 5 μM) and CYP3A4 (midazolam, 1 μM). All probe substrates were used at concentrations near or below their Kms. For experiment, a reaction mixture of test compound at 10 uM or in serial dilution, CYP probe substrate described above and 0.2 mg/mL pooled HLM in phosphate buffer, pH 7.4 in a final volume of 200 μL was pre-incubated at 37° C. for 10 minutes in triplicate. The reaction was initiated by addition of NADPH at final concentration of 1 mM. The reaction was terminated after 10 minutes (CYP1A2, CYP2D6 and CYP3A4) or 30 minutes (CYP2C9 and CYP2C19) by addition of 100 μL ice-cold acetonitrile with internal standard (IS). The samples were then centrifuged at 13,000 rpm and the supernatants were injected to LC-MS/MS (Agilent Technologies) to quantify the concentration of the specific metabolites of the probe substrates formed by individual CYP450 isoforms. The inhibition ratio is calculated as:(M t −M 0)/M water×100%in which Mt and M0 represent the concentrations of the specific probe substrate metabolite, which was formed by individual CYP450 isoform, at the beginning and end of the reaction in the presence of test compound; while Mwater represents the concentration of the specific metabolite at the end of the reaction in the absence of test compound. Test compound concentration-dependent response data experiments performed in triplicate. Mean CYP2D6 IC50 values were derived from non-linear, least-squares fitting of dose-dependent response data to a standard logistic equation (Prism, GraphPad Software, Inc)
- Assay organism: Homo sapiens
- Target name: Cytochrome P450 2D6
- Target type: SINGLE PROTEIN
- Target organism: Homo sapiens

## Reference Molecule A
- Canonical SMILES: FC(F)(F)c1ccc(CCN2CCC(Nc3ncnc4[nH]ncc34)C(F)(F)C2)cc1
- Properties:
- ChEMBL ID: CHEMBL5927039
- Molecular weight: 426.39
- Heavy atoms: 30
- Hydrogen bond donors: 2
- Hydrogen bond acceptors: 5
- TPSA: 69.73
- LogP: 3.74
- Rotatable bonds: 5
- Ring count: 4
- Aromatic rings: 3
- Formal charge: 0
- Fraction Csp3: 0.42
- QED: 0.61

## Known Reference Result on This Endpoint
- Molecule A clean result: median pChEMBL = 4.64
- This result is provided as context for predicting Molecule B on the same endpoint.

## Reference Molecule A Other ChEMBL Evidence
- type IC50; relation =; value 34100; units nM; pChEMBL 4.47; comment 715429
- type IC50; relation =; value 15200; units nM; pChEMBL 4.82; comment 715431

## Query Molecule B
- Canonical SMILES: FC(F)(F)c1ccc(C(F)(F)CN2CCC(Nc3ncnc4[nH]ncc34)CC2)cc1
- Properties:
- ChEMBL ID: CHEMBL6006710
- Molecular weight: 426.39
- Heavy atoms: 30
- Hydrogen bond donors: 2
- Hydrogen bond acceptors: 5
- TPSA: 69.73
- LogP: 4.04
- Rotatable bonds: 5
- Ring count: 4
- Aromatic rings: 3
- Formal charge: 0
- Fraction Csp3: 0.42
- QED: 0.6

## Molecule Similarity
- Weighted Tanimoto: 0.62

Answer: 6