Transforming growth factor β receptor-associated kinase 1 (TAK1) or mitogen activated-protein kinase kinase kinase 7 (MAP3K7) is a serine/threonine kinase which forms a key part of canonical immune and inflammatory signaling pathways. A 5-point pharmacophore model was developed and the generated pharmacophore model was used to derive a predictive atom-based 3D quantitative structure–activity relationship analysis (3D-QSAR) model for the studied dataset. The obtained 3D-QSAR model has an excellent correlation coefficient value (r² = 0.97) along with good statistical significance as shown by high Fisher ratio (F = 266.8). The QSAR model suggests that electron-withdrawing character, hydrogen bond-donating groups, hydrophobic and negative ionic groups positively contribute to the TAK1 inhibition.