## Endpoint to Predict
- Endpoint scope: assay
- Measurement type: IC50
- Label type: continuous
- Binary semantics: pchembl
- Assay description: TR-FRET Assay for ERBB Kinases: All compounds and PROTACs were serially diluted in three-fold increments using 100% DMSO, followed by an intermediate 10-fold dilution using Buffer A (50 mM HEPES, pH 7.5, 50 mM NaCl, 10 mM MgCl2, 1 mM DTT, and 0.1% Pluronic F-68). Two microliters of serially diluted compound or PROTAC were then transferred to black 384-well Proxiplates (PerkinElmer, #6008260) using an Integra Viaflo96. Next, 10 uL of protein kinase in Buffer A was added to each well of the assay plate and pre-incubated with compound for 10 minutes. Kinase reactions were then initiated by addition of 5 uL substrate mix containing 3 mM ATP and 30 uM fluorescein-labeled Poly-GluTyr (Thermo Fisher, #PV3610) in Buffer A and allowed to proceed for 10 minutes at room temperature. Reactions were quenched by addition of a 5 uL mixture containing 5 nM LanthaScreen® Tb-pY20 Antibody (Thermo Fisher, #PV3552) and 40 mM EDTA in Buffer A. Assay plates were then read using a Synergy2 (Biotek Instruments, Winooski, Vt.) via excitation thru a 340/20 nm bandpass filter and emission collected thru 490/10 nm (donor) and 520/25 nm (acceptor) bandpass filters. The final kinase concentrations used for each 15 uL reaction were as follows: 0.2 nM EGFR Exon20NPG (SignalChem, #E10-132GG), 0.1 nM wild type EGFR (BPS Bioscience, #40187), 0.3 nM EGFR L858R/T790M/C797S (BPS Bioscience, #40351), 0.1 nM EGFR L858R (BPS Bioscience, #40189), 0.4 nM L858R/T790M (BPS Bioscience, #40350), InM EGFR Dell9 (SignalChem, #E10-122JG), 10 nM EGFR Dell9 T790M (SignalChem, #E10-122KG), 0.3 nM Her2 (BPS Bioscience, #40230), 15 nM Her2 InsYVMA (SignalChem, #E27-13BG).
- Assay organism: Homo sapiens
- Target name: Receptor tyrosine-protein kinase erbB-3
- Target type: SINGLE PROTEIN
- Target organism: Homo sapiens

## Reference Molecule A
- Canonical SMILES: Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCCCOCCCCOCCCCOc2cc3ncnc(Nc4ccc(F)c(Cl)c4)c3cc2NC(=O)/C=C/CN(C)C)C(C)(C)C)cc1
- Properties:
- ChEMBL ID: CHEMBL5199166
- Molecular weight: 1086.77
- Heavy atoms: 76
- Hydrogen bond donors: 5
- Hydrogen bond acceptors: 14
- TPSA: 209.47
- LogP: 9
- Rotatable bonds: 29
- Ring count: 6
- Aromatic rings: 5
- Formal charge: 0
- Fraction Csp3: 0.48
- QED: 0.02

## Known Reference Result on This Endpoint
- Molecule A clean result: median pChEMBL = 5.18
- This result is provided as context for predicting Molecule B on the same endpoint.

## Reference Molecule A Other ChEMBL Evidence
- type IC50; relation =; value 6600; units nM; pChEMBL 5.18; comment 1030151

## Query Molecule B
- Canonical SMILES: COc1cc2ncnc(Nc3ccc(F)c(Cl)c3)c2cc1NC(=O)/C=C/CN(C)CCCOCCCOCC(=O)N[C@H](C(=O)N1CC(O)C[C@@H]1C(=O)NCc1ccc(-c2scnc2C)cc1)C(C)(C)C
- Properties:
- ChEMBL ID: CHEMBL5980554
- Molecular weight: 1002.61
- Heavy atoms: 70
- Hydrogen bond donors: 5
- Hydrogen bond acceptors: 14
- TPSA: 209.47
- LogP: 6.66
- Rotatable bonds: 23
- Ring count: 6
- Aromatic rings: 5
- Formal charge: 0
- Fraction Csp3: 0.42
- QED: 0.03

## Molecule Similarity
- Weighted Tanimoto: 0.83

Answer: 4.7