## Endpoint to Predict
- Endpoint scope: assay
- Measurement type: Ki
- Label type: continuous
- Binary semantics: pchembl
- Assay description: Fluorescence Resonance Energy Transfer (FRET) Assay: Test Example 1: Potency of test compounds were determined by measurement of their inhibition of BACE1 activity toward a fluorescent substrate. Experiments were performed by reference to the procedure as described in Ermolieff, et al. (Biochemistry 39:12450-12456 (2000), the teachings of which are incorporated hereby in their entirety). Briefly, the recombinant protease unit of BACE1 was prepared from E. coli expression as inclusion bodies, refolded, and purified as described in Lin, et al., (Proc. Nat. Acad. Sci. 97:1456-1460 (2000)). Fluorogenic substrate, MCA-SEVNLDAEFK(DNP)-NH2 (SEQ ID NO:1) was purchased. (M-2485, Bachem Americas, Torrance, Calif.). The substrate was derived from 10 amino acids of the human amyloid precursor protein (APP), with the Swedish variant amino acids at the beta-secretase cleavage site. The terminal amino acid was modified from arginine to lysine to facilitate derivatization with a functional group for detection by autofluorescence. The amino acid sequence of the "core" peptide of the substrate is SEVNLDAEFK (SEQ ID NO:2). The amino terminus was derivatized with (7-methoxycoumarin-4-yl)acetyl (MCA), and the epsilon amine of the lysine side chain of the terminal residue (K in sequence SEVNLDAEFK (SEQ ID NO:2)) was derivatized with 2,4-dinitrophenyl (DNP). Assays were performed in a buffer of 0.1 M sodium acetate, pH 4.4, 0.08% 3-[(3-Cholamidopropyl)dimethylammonio]propanesulfonate (CHAPS), 0.01% Tween80. BACE1 enzyme (final concentration 65 nM) was pre-incubated with test compounds for 15 minutes at room temperature. Fluorescence intensities were measured 60 minutes after addition of the substrate (final concentration 3 uM) by Tecan Safire2.
- Assay organism: Homo sapiens
- Target name: Beta-secretase 1
- Target type: SINGLE PROTEIN
- Target organism: Homo sapiens

## Reference Molecule A
- Canonical SMILES: NC1=NC2(CO1)c1cc(-c3cncnc3)ccc1OC(Cc1ccccc1)C21COC1
- Properties:
- ChEMBL ID: CHEMBL3650831
- Molecule type: Small molecule
- Molecular weight: 414.47
- Heavy atoms: 31
- Hydrogen bond donors: 1
- Hydrogen bond acceptors: 7
- TPSA: 91.85
- LogP: 2.7
- Rotatable bonds: 3
- Ring count: 6
- Aromatic rings: 3
- Formal charge: 0
- Fraction Csp3: 0.29
- QED: 0.71

## Known Reference Result on This Endpoint
- Molecule A clean result: median pChEMBL = 7
- This result is provided as context for predicting Molecule B on the same endpoint.

## Reference Molecule A Other ChEMBL Evidence
- type Ki; relation =; value 92.1; units nM; pChEMBL 7.04; comment 361641
- type Ki; relation =; value 113; units nM; pChEMBL 6.95; comment 361643

## Query Molecule B
- Canonical SMILES: CC1(C)Oc2ccc(NC(=O)c3ccc(Cl)cn3)cc2C2(COC(N)=N2)C12COC2
- Properties:
- ChEMBL ID: CHEMBL3703232
- Molecule type: Small molecule
- Molecular weight: 428.88
- Heavy atoms: 30
- Hydrogen bond donors: 2
- Hydrogen bond acceptors: 7
- TPSA: 108.06
- LogP: 2.72
- Rotatable bonds: 2
- Ring count: 5
- Aromatic rings: 2
- Formal charge: 0
- Fraction Csp3: 0.38
- QED: 0.76

## Molecule Similarity
- Weighted Tanimoto: 0.32

Answer: 7.42