## Endpoint to Predict
- Endpoint scope: assay
- Measurement type: IC50
- Label type: continuous
- Binary semantics: pchembl
- Assay description: Kinase assay: KINOMEscan is based on a competition binding assay that quantitatively measures the ability of a compound to compete with an immobilized, active-site directed ligand. The assay is performed by combining three components: DNA-tagged kinase; immobilized ligand; and a test compound. The ability of the test compound to compete with the immobilized ligand is measured via quantitative PCR of the DNA tag.For most assays, kinase-tagged T7 phage strains were prepared in an E. coli host derived from the BL21 strain. E. coli were grown to log-phase and infected with T7 phage and incubated with shaking at 32° C. until lysis. The lysates were centrifuged and filtered to remove cell debris. The remaining kinases were produced in HEK-293 cells and subsequently tagged with DNA for qPCR detection. Streptavidin-coated magnetic beads were treated with biotinylated small molecule ligands for 30 minutes at room temperature to generate affinity resins for kinase assays. The liganded beads were blocked with excess biotin and washed with blocking buffer (SeaBlock (Pierce), 1% BSA, 0.05% Tween 20, 1 mM DTT) to remove unbound ligand and to reduce nonspecific binding. Binding reactions were assembled by combining kinases, liganded affinity beads, and test compounds in 1× binding buffer (20% SeaBlock, 0.17×PBS, 0.05% Tween 20, 6 mM DTT). All reactions were performed in polystyrene 96-well plates in a final volume of 0.14 ml. The assay plates were incubated at room temperature with shaking for 1 hour and the affinity beads were washed with wash buffer (1×PBS, 0.05% Tween 20). The beads were then re-suspended in elution buffer (1×PBS, 0.05% Tween 20, 0.5 M non-biotinylated affinity ligand) and incubated at room temperature with shaking for 30 minutes. The kinase concentration in the eluates was measured by qPCR.
- Assay organism: Homo sapiens
- Target name: Receptor tyrosine-protein kinase erbB-4
- Target type: SINGLE PROTEIN
- Target organism: Homo sapiens

## Reference Molecule A
- Canonical SMILES: N#Cc1cnc2ccc(NC(=O)C3CSSC3)cc2c1Nc1ccc(OCc2cccc(F)c2)c(Cl)c1
- Properties:
- ChEMBL ID: CHEMBL4441244
- Molecule type: Unknown
- Molecular weight: 551.07
- Heavy atoms: 37
- Hydrogen bond donors: 2
- Hydrogen bond acceptors: 7
- TPSA: 87.04
- LogP: 7.17
- Rotatable bonds: 7
- Ring count: 5
- Aromatic rings: 4
- Formal charge: 0
- Fraction Csp3: 0.15
- QED: 0.24

## Known Reference Result on This Endpoint
- Molecule A clean result: median pChEMBL = 6.26
- This result is provided as context for predicting Molecule B on the same endpoint.

## Reference Molecule A Other ChEMBL Evidence
- type IC50; relation =; value 550; units nM; pChEMBL 6.26; comment 742585

## Query Molecule B
- Canonical SMILES: N#Cc1cnc2cc(OC[C@H](O)CO)c(NC(=O)CC3CSSC3)cc2c1Nc1ccc(OCc2cccc(F)c2)c(Cl)c1
- Properties:
- ChEMBL ID: CHEMBL4642574
- Molecule type: Unknown
- Molecular weight: 655.17
- Heavy atoms: 44
- Hydrogen bond donors: 4
- Hydrogen bond acceptors: 10
- TPSA: 136.73
- LogP: 6.29
- Rotatable bonds: 12
- Ring count: 5
- Aromatic rings: 4
- Formal charge: 0
- Fraction Csp3: 0.26
- QED: 0.13

## Molecule Similarity
- Weighted Tanimoto: 0.66

Answer: 7.3