## Endpoint to Predict
- Endpoint scope: assay
- Measurement type: IC50
- Label type: continuous
- Binary semantics: pchembl
- Assay description: Fluorescence Quench Assay: The inhibitory activity of compounds was assessed by a fluorescence quench assay of BACE1 activity using commercially available substrate HiLyte Fluor 488-Glu-Val-Asn-Leu-Asp-Ala-Glu-Phe-Lys-(QXL 520)-OH (SEQ ID NO:1) AnaSpec, San Jose, Calif.) and truncated human beta-secretase, BACE1 (amino acids 1-454) fused to a myc-his tag and secreted from HEK293/BACEect. cells into OptiMEM (Invitrogen). The substrate was dissolved at 1 mg/ml in DMSO.The assay was performed in the presence of OptiMEM (supernatant collected over 24 h and cleared from cellular debris by centrifugation) containing the ectodomain of BACE1, 25 ul water containing the desired 2-fold concentration of test compound and 2% DMSO, 1 uM substrate peptide, 20 mM NaOAc, pH 4.4, and 0.04% Triton-X100 in a total assay volume of 50 ul in a 384 well plate. In general, 25 ul of compound dilution were given to the plate followed by the addition of 10 ul of BACE1 containing OptiMEM diluted 1:10 in water with 0.2% Triton X-100. The reaction was started with the addition of 15 ul substrate in NaOAc buffer. The reaction was incubated at rt (dark) in an Envision multilabel reader (Perkin Elmer) and the cleavage of the substrate was recorded as kinetic for 60 min at ex: 485 nm, em: 538 nm. Blank wells containing no enzyme were included on each plate. The intensity of fluorescence was regressed against time in order to derive velocities of reaction in all 384 wells. These velocities were used for calculating percent control using an uninhibited control containing 1% DMSO as 100% and blank control performed in the absence of enzyme as 0%. IC50 values were calculated by fitting percent control vs. test compound concentration using Assay Explorer.
- Target name: Beta-secretase 1
- Target type: SINGLE PROTEIN
- Target organism: Homo sapiens

## Reference Molecule A
- Canonical SMILES: CO[C@H]1[C@H](C)C[C@@]2(Cc3ccc(C#N)cc3[C@]23N=C(N)N(C2COC2)C3=O)C[C@@H]1C
- Properties:
- ChEMBL ID: CHEMBL4112862
- Molecule type: Small molecule
- Molecular weight: 408.5
- Heavy atoms: 30
- Hydrogen bond donors: 1
- Hydrogen bond acceptors: 6
- TPSA: 100.94
- LogP: 1.93
- Rotatable bonds: 2
- Ring count: 5
- Aromatic rings: 1
- Formal charge: 0
- Fraction Csp3: 0.61
- QED: 0.81

## Known Reference Result on This Endpoint
- Molecule A clean result: median pChEMBL = 8.52
- This result is provided as context for predicting Molecule B on the same endpoint.

## Reference Molecule A Other ChEMBL Evidence
- type IC50; relation =; value 3; units nM; pChEMBL 8.52; comment 451990

## Query Molecule B
- Canonical SMILES: CO[C@H]1[C@H](C)C[C@@]2(Cc3ccc(C#N)cc3[C@]23N=C(N)N(CC2(C)COC2)C3=O)C[C@@H]1C
- Properties:
- ChEMBL ID: CHEMBL4109666
- Molecule type: Small molecule
- Molecular weight: 436.56
- Heavy atoms: 32
- Hydrogen bond donors: 1
- Hydrogen bond acceptors: 6
- TPSA: 100.94
- LogP: 2.57
- Rotatable bonds: 3
- Ring count: 5
- Aromatic rings: 1
- Formal charge: 0
- Fraction Csp3: 0.64
- QED: 0.78

## Molecule Similarity
- Weighted Tanimoto: 0.74

Answer: 8.4