A three-dimensional pharmacophore model of two types of HER2 inhibitors was obtained by using the CATALYST software. Although these inhibitors including 19 compounds of benzylidene malononitrile family and 13 compounds of 3-substituted indolin-2-ones family, possess quite different structures,a common pharmacophore model with very good stratistical results was determined. The common pharmacophore model included a hydrogen-bonding receptor, a hydrogen- bonding donor, an aliphatic hydrophobic core and and aromatic hydrophobic core. The results uncovered that these two types of molecules would take the similar pattern when they interact with the receptor. Based on the pharmacophore model a novel 3D-QSAR analysis was conducted, which showed very good predicitive ability (which linear correlation coefficient r≈0.96). This pharmacophore model is very useful for clarifying the structure-activity relationships of HER2 inhibitors and evaluateing new potential leading compounds.

Key words: KINASE, ROWTH FACTOR, BENZYL GROUP P, PROPANEDINITRILE P, QUANTITATIVE STRUCTURE ACTIVITY RELATIONSHIP, INHIBITOR, TYROSINASE