## Endpoint to Predict
- Endpoint scope: assay
- Measurement type: IC50
- Label type: continuous
- Binary semantics: pchembl
- Assay description: Kinase Inhibiting Activity: A reaction buffer (100 mM HEPES (pH 7.4), 10 mM MgCl2, 0% Brij-35, 0% Tween-20, and 1 mM DTT) was mixed with a RET recombinant protein (RETwild type; Invitrogen # PV3819, final concentration: 80 pg/ul, or a RETGatekeeper mutation (V804L); Invitrogen # PV4397, final concentration: 80 pg/ul) to prepare a RET kinase solution. The test compound was prepared to have a final concentration of 4000 nm with DMSO, and further, test compound samples at 12 different concentrations were prepared with a dilution magnification of √10. 19 uL of the RET kinase solution was added to each of lines A to P of a 384-well plate, and thereafter, the test compound at each concentration was added to lines C to N, and further, 1 uL of dimethyl sulfoxide (hereinafter referred to as DMSO) was added to each of lines A, B, O and P. Thereafter, the obtained mixtures were each preincubated at room temperature for 20 minutes. Furthermore, a substrate solution A containing ATP (final concentration: 1 mM) and a substrate solution B containing no ATP, both in addition to a reaction buffer and FL-Peptide 22 (PerkinElmer, #760366, final concentration: 1.5 uM) were produced. The substrate solution A was added in an amount of 5 uL to lines B to 0, whereas the substrate solution B was added in an amount of 5 uL to lines A and P. The obtained mixtures were each incubated at 28° C. for 45 minutes. A reaction termination solution (100 mM HEPES (pH 7.4), 0.01% Briji-35, 40 mM EDTA, and 0.1% Coating Reagent 3) was added in an amount of 40 ul to the reaction mixture, so as to terminate the reaction.
- Assay organism: Homo sapiens
- Target name: Proto-oncogene tyrosine-protein kinase receptor Ret
- Target type: SINGLE PROTEIN
- Target organism: Homo sapiens

## Reference Molecule A
- Canonical SMILES: CCc1cc2c(cc1N1CCC(N3CCOCC3)CC1)C(C)(C)c1[nH]c3cc(C#N)ccc3c1C2=O
- Properties:
- ChEMBL ID: CHEMBL1738797
- Preferred name: ALECTINIB
- Molecule type: Small molecule
- Max clinical phase: 4
- Molecular weight: 482.63
- Heavy atoms: 36
- Hydrogen bond donors: 1
- Hydrogen bond acceptors: 5
- TPSA: 72.36
- LogP: 4.77
- Rotatable bonds: 3
- Ring count: 6
- Aromatic rings: 3
- Formal charge: 0
- Fraction Csp3: 0.47
- QED: 0.58

## Known Reference Result on This Endpoint
- Molecule A clean result: median pChEMBL = 7.28
- This result is provided as context for predicting Molecule B on the same endpoint.

## Reference Molecule A Other ChEMBL Evidence
- type IC50; relation =; value 52; units nM; pChEMBL 7.28; comment 985948

## Query Molecule B
- Canonical SMILES: COc1cc2cc(-c3ccc(CC(=O)Nc4cc(C(C)(C)C(F)(F)F)no4)cn3)cnc2cc1OC
- Properties:
- ChEMBL ID: CHEMBL5095497
- Preferred name: ZETELETINIB
- Molecule type: Small molecule
- Max clinical phase: 1
- Molecular weight: 500.48
- Heavy atoms: 36
- Hydrogen bond donors: 1
- Hydrogen bond acceptors: 7
- TPSA: 99.37
- LogP: 5.32
- Rotatable bonds: 7
- Ring count: 4
- Aromatic rings: 4
- Formal charge: 0
- Fraction Csp3: 0.28
- QED: 0.37

## Molecule Similarity
- Weighted Tanimoto: 0.09

Answer: 8.34