## Endpoint to Predict
- Endpoint scope: assay
- Measurement type: IC50
- Label type: continuous
- Binary semantics: pchembl
- Assay description: TYK2 Kinase Domain Enzymatic Activity Assay: A reaction buffer containing the following components: an enzyme buffer (1×), 5 mM MgCl, 1 mM DTT, 10 nM SEB (Cisbio, Cat. No. 61SEBALB), 0.62 mM EGTA and 0.01% Brij35 from the kit; a human recombinant TYK2 kinase (JH1) domain protein (Carna Biosciences, Cat. No. 08-147) diluted to a solution of 0.25 ng/μL with the reaction buffer; a substrate reaction solution containing 11.25 μM ATP and a biotinylated tyrosine kinase substrate diluted to 0.5 μM with the reaction buffer; a detection solution containing 0.1 ng/μL Eulabeled cage antibody (Cisbio, Cat. No. 61T66KLB) and 25 nM streptavidin-labeled XL665 (Cisbio, Cat. No. 610SAXLB) in the reaction buffer. The test compound is dissolved to 1 mM in DMSO, followed by a serial 4-fold dilution with DMSO to a minimum concentration of 61 nM. Each concentration is further diluted 40-fold with the reaction buffer. To a 384-well assay plate (Corning, Cat. No. 3674) are added 4 μL of compound solution and 2 μL of TYK2 kinase solution. The mixture is incubated at room temperature for 15 minutes, and then added with 4 μL of the substrate reaction solution. After further incubation at room temperature for 40 minutes, the reaction mixture is added with an equal volume of 10 μL detection solution and allowed to stand at room temperature for 30 minutes. An Envision plate reader (Perkin Elmer) is then used to measure the progress of the reaction at 620 nm and 665 nm. The ratio of absorbances at 665 nm and 620 nm is positively correlated with the degree of substrate phosphorylation, therefore the activity of TYK2 kinase is detected.
- Assay organism: Homo sapiens
- Target name: Non-receptor tyrosine-protein kinase TYK2
- Target type: SINGLE PROTEIN
- Target organism: Homo sapiens

## Reference Molecule A
- Canonical SMILES: CNC(=O)c1nnc(NC(=O)C2CC2)cc1Nc1cccc(-c2ncn(C)n2)c1OC
- Properties:
- ChEMBL ID: CHEMBL4596392
- Preferred name: CRAVACITINIB
- Molecule type: Small molecule
- Max clinical phase: 4
- Molecular weight: 422.45
- Heavy atoms: 31
- Hydrogen bond donors: 3
- Hydrogen bond acceptors: 8
- TPSA: 135.95
- LogP: 1.73
- Rotatable bonds: 7
- Ring count: 4
- Aromatic rings: 3
- Formal charge: 0
- Fraction Csp3: 0.3
- QED: 0.52

## Known Reference Result on This Endpoint
- Molecule A clean result: median pChEMBL = 5.61
- This result is provided as context for predicting Molecule B on the same endpoint.

## Reference Molecule A Other ChEMBL Evidence
- type IC50; relation =; value 2100; units nM; pChEMBL 5.68; comment 1257772
- type IC50; relation =; value 2900; units nM; pChEMBL 5.54; comment 1257792

## Query Molecule B
- Canonical SMILES: CNC(=O)c1nnc(NC(=O)[C@@H]2CC2(F)F)cc1Nc1cccc(-c2ncn(C)n2)c1OC
- Properties:
- ChEMBL ID: CHEMBL5964910
- Molecular weight: 458.43
- Heavy atoms: 33
- Hydrogen bond donors: 3
- Hydrogen bond acceptors: 8
- TPSA: 135.95
- LogP: 1.98
- Rotatable bonds: 7
- Ring count: 4
- Aromatic rings: 3
- Formal charge: 0
- Fraction Csp3: 0.3
- QED: 0.49

## Molecule Similarity
- Weighted Tanimoto: 0.84

Answer: 5.11