## Endpoint to Predict
- Endpoint scope: assay
- Measurement type: IC50
- Label type: continuous
- Binary semantics: pchembl
- Assay description: Inhibition Assay of Human DPPI (Cathepsin C): Materials: Microtiterplates (Optiplate-384 F) were purchased from PerkinElmer (Prod. No. 6007270). The substrate Gly-Arg-AMC was from Biotrend (Prod.-No. 808756 Custom peptide). Bovine serum albumin (BSA; Prod. No. A3059) and Dithiothreitol (DTT; Prod. No D0632) were from Sigma. TagZyme buffer was from Riedel-de-Haen (Prod.-No. 04269), NaCl was from Merck (Prod.-No. 1.06.1000) and morpholinoethane sulfonic acid (MES), was from Serva (Prod.-No. 29834). The DPP1 inhibitor Gly-Phe-DMK was purchased from MP Biomedicals (Prod.-No. 03DK00625). The recombinant human DPPI was purchased from Prozymex. All other materials were of highest grade commercially available. The following buffers were used: MES buffer: 25 mM MES, 50 mM NaCl, 5 mM DTT, adjusted to pH 6, containing 0.1% BSA; TAGZyme Buffer: 20 mM NaH2PO4, 150 mM NaCl adjusted to pH 6 with HCl. Assay conditions: The recombinant human DPPI was diluted in TAGZyme buffer to 1 U/ml (38.1 μg/ml, respectively), and then activated by mixing in a 1:2 ratio with a Cysteamine aqueous solution (2 mM) and incubating for 5 min at room temperature. Five uL test compound (final concentration 0.1 nM to 100 μM) in aqua bidest (containing 4% DMSO, final DMSO concentration 1%) were mixed with 10 μL of DPPI in MES buffer (final concentration 0.01 ng/μL) and incubated for 10 min. Then, 5 μL of substrate in MES buffer (final concentration 50 μM) were added. The microtiter plates were then incubated at room temperature for 30 mM Then, the reaction was stopped by adding 10 μL of Gly-Phe-DMK in MES-buffer (final concentration 1 μM). The fluorescence in the wells was determined using a Molecular Devices SpectraMax M5 Fluorescence Reader (Ex 360 nm, Em 460 nm) or an Envision Fluorescence Reader (Ex 355 nm, Em 460 nm). Each assay microtiter plate contained wells with vehicle controls (1% DMSO in bidest+0.07% BSA) as reference for non-inhibited enzyme activity (100% Ctl; high values) and wells with inhibitor (Gly-Phe-DMK, in bidest+1% DMSO+0.07% BSA, final concentration 1 μM) as controls for background fluorescence (0% Ctl; low values). The analysis of the data was performed by calculating the percentage of fluorescence in the presence of test compound in comparison to the fluorescence of the vehicle control after subtracting the background fluorescence using the following formula: (RFU(sample)−RFU(background))*100/(RFU(control)−RFU(background)).
- Assay organism: Homo sapiens
- Target name: Dipeptidyl peptidase 1
- Target type: SINGLE PROTEIN
- Target organism: Homo sapiens

## Reference Molecule A
- Canonical SMILES: COCC(=O)n1cc(-c2ccc(C[C@@H](C#N)NC(=O)[C@H]3N[C@@H]4CC[C@H]3C4)c(F)c2)cn1
- Properties:
- ChEMBL ID: CHEMBL3662601
- Molecule type: Small molecule
- Molecular weight: 425.46
- Heavy atoms: 31
- Hydrogen bond donors: 2
- Hydrogen bond acceptors: 6
- TPSA: 109.04
- LogP: 1.67
- Rotatable bonds: 7
- Ring count: 4
- Aromatic rings: 2
- Formal charge: 0
- Fraction Csp3: 0.45
- QED: 0.7

## Known Reference Result on This Endpoint
- Molecule A clean result: median pChEMBL = 7.85
- This result is provided as context for predicting Molecule B on the same endpoint.

## Reference Molecule A Other ChEMBL Evidence
- type IC50; relation =; value 14.2; units nM; pChEMBL 7.85; comment 500274

## Query Molecule B
- Canonical SMILES: CN1CCN(C(=O)c2ccc(-c3ccc(C[C@@H](C#N)NC(=O)[C@H]4N[C@@H]5CC[C@H]4C5)c(F)c3)cc2)CC1
- Properties:
- ChEMBL ID: CHEMBL3662698
- Molecule type: Small molecule
- Molecular weight: 489.6
- Heavy atoms: 36
- Hydrogen bond donors: 2
- Hydrogen bond acceptors: 5
- TPSA: 88.47
- LogP: 2.57
- Rotatable bonds: 6
- Ring count: 5
- Aromatic rings: 2
- Formal charge: 0
- Fraction Csp3: 0.46
- QED: 0.65

## Molecule Similarity
- Weighted Tanimoto: 0.62

Answer: 8.05