## 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 LANCES 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: CC(=O)C1CCC[C@H](C)[C@@H](C)S(=O)(=O)NC(=O)c2ccc3c(c2)N(C[C@@H]2CC[C@@H]12)C[C@@]1(CCCc2cc(Cl)ccc21)CO3
- Properties:
- ChEMBL ID: CHEMBL5841041
- Molecular weight: 627.25
- Heavy atoms: 43
- Hydrogen bond donors: 1
- Hydrogen bond acceptors: 6
- TPSA: 92.78
- LogP: 6.31
- Rotatable bonds: 1
- Ring count: 6
- Aromatic rings: 2
- Formal charge: 0
- Fraction Csp3: 0.59
- QED: 0.4

## Known Reference Result on This Endpoint
- Molecule A clean result: median pChEMBL = 9.47
- This result is provided as context for predicting Molecule B on the same endpoint.

## Reference Molecule A Other ChEMBL Evidence
- type IC50; relation =; value 0.34; units nM; pChEMBL 9.47; comment 1151779

## Query Molecule B
- Canonical SMILES: C[C@@H]1[C@@H](C)C/C=C\[C@H](CN2CCN3CCOC[C@@H]3C2)[C@@H]2CC[C@H]2CN2C[C@@]3(CCCc4cc(Cl)ccc43)COc3ccc(cc32)C(=O)NS1(=O)=O
- Properties:
- ChEMBL ID: CHEMBL5740846
- Molecular weight: 737.41
- Heavy atoms: 51
- Hydrogen bond donors: 1
- Hydrogen bond acceptors: 8
- TPSA: 91.42
- LogP: 5.52
- Rotatable bonds: 2
- Ring count: 8
- Aromatic rings: 2
- Formal charge: 0
- Fraction Csp3: 0.62
- QED: 0.4

## Molecule Similarity
- Weighted Tanimoto: 0.64

Answer: 9.54