## Endpoint to Predict
- Endpoint scope: assay
- Measurement type: IC50
- Label type: continuous
- Binary semantics: pchembl
- Assay description: Cell Free Mcl-1: Bim Affinity Assay (Mcl-1 HTRF): The inhibition of the Mcl-1/Bim interaction was measured using a time-resolved fluorescence resonance energy transfer (TR-FRET) assay. The recombinant human Mcl-1 (C-terminally 6×His tagged Mcl-1 containing residues 171-327) was generated at Amgen Inc (Thousand Oaks, Calif.). A biotinylated peptide derived from human Bim (residues 51-76) was purchased from CPC Scientific (San Jose, Calif.). The TR-FRET assay was conducted in a 384-well white OptiPlate (PerkinElmer, Waltham, Mass.) in a total volume of 40 μL. The reaction mixture contained 0.1 nM Mcl-1(171-327), 0.05 nM biotin-Bim(51-76), 0.05 nM LANCER Eu-W1024 Anti-6×His (PerkinElmer), 0.07 nM Streptavidin-Xlent (Cisbio, Bedford, Mass.), and serially diluted test compounds in the binding buffer of 20 mM Hepes, pH 7.5, 150 mM NaCl, 0.02 mM Brij©35, and 1 mM dithiothreitol. Test compounds were pre-incubated with Mcl-1(171-327) and biotin-Bim (51-76) for 60 min before addition of the detection mixture (LANCE Eu-W1024 Anti-6×His and Streptavidin-Xlent). The reaction plates were further incubated overnight and then were read on an Envision® multimode reader (PerkinElmer). Fluorescence signals were measured at 620 nm (40-nm bandwidth) and 665 nm (7.5-nm bandwidth) with a 60 μs delay after excitation at 320 nm (75-nm bandwidth). The signal ratio at 665/620 nm corresponded to the Mcl-1/Bim interaction and was used in all data analyses. The IC50 values of test compounds were determined from duplicate data by analyzing competition curves using a four-parameter sigmoidal model in GraphPad Prism (GraphPad Software, San Diego, Calif.) or in Genedata Screener® (Genedata, Basel, Switzerland).
- Target name: Induced myeloid leukemia cell differentiation protein Mcl-1/Bcl-2-like protein 11
- Target type: PROTEIN-PROTEIN INTERACTION
- Target organism: Homo sapiens

## Reference Molecule A
- Canonical SMILES: C[C@@H]1[C@@H](C)CCC[C@@H]([C@H]2OC[C@H](N)CO2)[C@@H]2CC[C@H]2CN2C[C@@]3(CCCc4cc(Cl)ccc43)COc3ccc(cc32)C(=O)NS1(=O)=O
- Properties:
- ChEMBL ID: CHEMBL5960375
- Molecular weight: 686.32
- Heavy atoms: 47
- Hydrogen bond donors: 2
- Hydrogen bond acceptors: 8
- TPSA: 120.19
- LogP: 5.42
- Rotatable bonds: 1
- Ring count: 7
- Aromatic rings: 2
- Formal charge: 0
- Fraction Csp3: 0.64
- QED: 0.41

## Known Reference Result on This Endpoint
- Molecule A clean result: median pChEMBL = 8.86
- This result is provided as context for predicting Molecule B on the same endpoint.

## Reference Molecule A Other ChEMBL Evidence
- type IC50; relation =; value 1.37; units nM; pChEMBL 8.86; comment 1177666

## Query Molecule B
- Canonical SMILES: CC[C@@H]1CCCC[C@H]([C@H]2OC[C@@H](N(C)C)CO2)[C@@H]2CC[C@H]2CN2C[C@@]3(CCCc4cc(Cl)ccc43)COc3ccc(cc32)C(=O)NS1(=O)=O
- Properties:
- ChEMBL ID: CHEMBL6010413
- Molecular weight: 714.37
- Heavy atoms: 49
- Hydrogen bond donors: 1
- Hydrogen bond acceptors: 8
- TPSA: 97.41
- LogP: 6.17
- Rotatable bonds: 3
- Ring count: 7
- Aromatic rings: 2
- Formal charge: 0
- Fraction Csp3: 0.66
- QED: 0.4

## Molecule Similarity
- Weighted Tanimoto: 0.73

Answer: 9.45