## Endpoint to Predict
- Endpoint scope: assay
- Measurement type: Ki
- Label type: continuous
- Binary semantics: pchembl
- Assay description: Kat6B Assay 2: A. Compound preparation 1. Prepare 10 mM stock solutions in 100% DMSO from solid material 2. Serial dilute 10 mM, 1 mM or 0.1 mM compound stocks 3-fold in 100% DMSO for 11-point dose responseB. Reagent preparation 1. Prepare 1× assay buffer containing 10 mM Tris HCL pH 8, 2.5 mM NaCl, 0.5 mM EDTA, 0.01% BSG and 0.02% Tween-20 2. Dilute Histone peptide (CPC Scientific) and AcCoA (Sigma) together in assay buffer to 2×. 3. Dilute KAT enzyme in assay buffer to 2×.C. Enzyme reaction 1. Final reaction conditions for each KAT assay in a 20 ul assay reaction volume: KAT6B 25 nM, 25 uM AcCoA, 2 uM H3 1-21 peptide, 60-minute reaction 2. Add 0.5 ul of diluted compound to the assay plate (384-well V-bottom polypropylene plates) or 0.5 ul of DMSO for control wells. 3. Add 10 ul of 2× Histone peptide/2×AcCoA mix to the assay plate. 4. Add 10 ul of 2× enzyme to the assay plate. 5. Stop the reaction after the indicated time with the addition of 2 ul of 5% formic acid 6. Each reaction was analyzed using self-assembled monolayer desorption/ionization time-of-flight mass spectrometry (Mrksich, Milan (2008) Mass Spectrometry of Self-Assembled Monolayers: A New Tool for Molecular Surface Science ACS Nano 2008 2 (1), 7-18; SAMDI Tech, Inc. (Chicago, Ill.)). 7. Area under the curve (AUC) for both substrate and product peaks was determined for KAT5 at M.W. 2561 [Substrate+H]+ and 2603 [Product+H]+ with a +/−1 Da tolerance, respectively 8. Area under the curve (AUC) for both substrate and product peaks was determined for KAT6a, KAT6B, KAT7 and KAT8 at M.W. 2723 [Substrate+H]+ and 2765 [Product+H]+ with a +/−1 Da tolerance, respectively. 9. Percent conversion to product was calculated by: AUCProduct/(AUCsubstrate+AUCProduct).D. Data analysis 1. IC50 values were determined by fitting the % conversion at each inhibitor concentration to the 4-parameter IC50 equation using Pfizer proprietary curve fitting software. 2. Ki values were determined by fitting the % conversion at each inhibitor concentration to the Morrison equation for tightbinding competitive inhibitors using Pfizer proprietary curve fitting software.
- Target name: Histone acetyltransferase KAT6B
- Target type: SINGLE PROTEIN
- Target organism: Homo sapiens

## Reference Molecule A
- Canonical SMILES: COc1cc(Cn2cccn2)cc2onc(NS(=O)(=O)c3ccc(C)cc3F)c12
- Properties:
- ChEMBL ID: CHEMBL5808891
- Molecular weight: 416.43
- Heavy atoms: 29
- Hydrogen bond donors: 1
- Hydrogen bond acceptors: 6
- TPSA: 99.25
- LogP: 3.33
- Rotatable bonds: 6
- Ring count: 4
- Aromatic rings: 4
- Formal charge: 0
- Fraction Csp3: 0.16
- QED: 0.52

## Known Reference Result on This Endpoint
- Molecule A clean result: median pChEMBL = 7.92
- This result is provided as context for predicting Molecule B on the same endpoint.

## Reference Molecule A Other ChEMBL Evidence
- type Ki; relation =; value 12.1; units nM; pChEMBL 7.92; comment 1223896

## Query Molecule B
- Canonical SMILES: COc1cc(Cn2cccn2)cc2onc(NS(=O)(=O)c3ccccc3CO)c12
- Properties:
- ChEMBL ID: CHEMBL5963038
- Molecular weight: 414.44
- Heavy atoms: 29
- Hydrogen bond donors: 2
- Hydrogen bond acceptors: 7
- TPSA: 119.48
- LogP: 2.37
- Rotatable bonds: 7
- Ring count: 4
- Aromatic rings: 4
- Formal charge: 0
- Fraction Csp3: 0.16
- QED: 0.48

## Molecule Similarity
- Weighted Tanimoto: 0.71

Answer: 8.81