The relationship between the topochemical indices and cyclin-dependent kinase 2 (CDK2) inhibitory activity of indole-2-ones has been investigated. The relationship of topochemical versions of well known topological indices of Wiener's index--a distance-based topological descriptor, molecular connectivity index, an adjacency-based topological descriptor and eccentric connectivity index--an adjacency-cum-distance based topological descriptor with CDK2 inhibitory activity of indole-2-ones has been investigated. A data set comprising 67 analogues of substituted indole-2-ones was selected for the present investigation. The values of the Wiener's topochemical index, molecular connectivity topochemical index and eccentric connectivity topochemical index for each of 67 analogues comprising the data set were computed. The resulting data was analyzed and suitable models developed after identification of the active ranges. Subsequently, a biological activity was assigned to each analogue in the data set using these models, which was then compared with the reported CDK2 inhibitory activity. Accuracy of prediction was found to vary from a minimum of 88% for a model based upon molecular connectivity topochemical index to a maximum of approximately 90% for model based upon eccentric connectivity topochemical index.