## Endpoint to Predict
- Endpoint scope: assay
- Measurement type: IC50
- Label type: continuous
- Binary semantics: pchembl
- Assay description: POP Inhibition Assays: POP activity was determined following the method described by Toide et al (Toide K et al., J. Pharmacol. Exp. Ther. 1995; 274:1370-8), using Z-G-P-AMC (N-benzyloxycarbonyl-Gly-Pro-methylcoumarinyl-7-amide) as POP substrate. The reactions were performed in 96-well microtiter plates, which allowed simultaneous monitoring of multiple reactions. For each reaction, activity buffer (134 μl, 100 mM Na/K phosphate buffer, pH 8) was pre-incubated for 15 min at 37° C. with hPOP (ranging from 20 to 60 nM, depending on the activity of the hPOP batch) and the corresponding new compound solution (3 μl). A stock solution of new compound was prepared in DMSO (100 mM), and dilutions were prepared from this stock solution with DMSO. Alternatively, the reactions were performed using another activity buffer (141 μL, 100 mM Tris-acetate, 10 mM BSA, 1 mM DTT, pH 7.3), pre-incubating with hPOP (10 nM) and the corresponding new compound solution (3 μl) (Conditions B).After preincubation, Z-G-P-AMC (10 μl, 3 mM in 40% 1,4-dioxane) was added (3 μl, 1.5 mM in 40% of 1,4-dioxane, in Conditions B), and the reaction was incubated for 1 hour at 37° C. The reaction was stopped by adding sodium acetate (150 μl, 1 M, pH 4) and the formation of AMC was measured fluorimetrically. The excitation and emission wavelengths were 360/40 and 485/20 nm, respectively.Several concentration points (ranging from 25 μM to 400 μM) were measured for each compound. The inhibitory activity on prolyl oligopeptidase was calculated according to eq 1. For each new compound, the fluorescence in the presence (a) and in the absence of hPOP (b) was measured. The maximum fluorescence (0% inhibitory activity) was obtained from a sample of hPOP in the absence of inhibitory compounds. To estimate the inhibitory potency of the novel compound, activities were plotted against the log concentration of the compound, adjusting to a sigmoid curve using GraphPad Prism software, and the IC50 value, defined as the concentration of compound required to inhibit 50% of POP activity, was determined from the resulting curve.
- Target name: Unchecked
- Target type: UNCHECKED

## Reference Molecule A
- Canonical SMILES: COc1cc(C(=O)N2CC(F)(F)C[C@H]2C(=O)N2CCC[C@H]2C#N)cc(OC)c1OC(=O)c1ccccc1
- Properties:
- ChEMBL ID: CHEMBL5744339
- Molecular weight: 513.5
- Heavy atoms: 37
- Hydrogen bond donors: 0
- Hydrogen bond acceptors: 7
- TPSA: 109.17
- LogP: 3.29
- Rotatable bonds: 6
- Ring count: 4
- Aromatic rings: 2
- Formal charge: 0
- Fraction Csp3: 0.38
- QED: 0.43

## Known Reference Result on This Endpoint
- Molecule A clean result: median pChEMBL = 6.96
- This result is provided as context for predicting Molecule B on the same endpoint.

## Reference Molecule A Other ChEMBL Evidence
- type IC50; relation =; value 111; units nM; pChEMBL 6.96; comment 571481

## Query Molecule B
- Canonical SMILES: N#C[C@@H]1CCCN1C(=O)[C@@H]1CC(F)(F)CN1C(=O)c1ccc(OCc2ccccc2)cc1
- Properties:
- ChEMBL ID: CHEMBL5759422
- Molecular weight: 439.46
- Heavy atoms: 32
- Hydrogen bond donors: 0
- Hydrogen bond acceptors: 4
- TPSA: 73.64
- LogP: 3.63
- Rotatable bonds: 5
- Ring count: 4
- Aromatic rings: 2
- Formal charge: 0
- Fraction Csp3: 0.38
- QED: 0.71

## Molecule Similarity
- Weighted Tanimoto: 0.62

Answer: 6.54