Hastening natural product-based therapeutics for cancer treatment using in silico strategy

Tankyrases are multifunctional polymerases proteins that regulate numerous cellular processes including Wnt signaling, telomere maintenance and tumor suppressors. Therefore, tankyrases are characterized to be an effective target for the management of numerous cancers. Despite the number of available inhibitors, the on-target intestinal toxicity serves as the major challenge in developing new drugs against TNKS1 protein. Considering the same, in the present study, an effort has been made to identify novel and potent inhibitors from the NPACT library by employing various computational approaches. The results from our analysis revealed that obovaten and duartin exhibit a higher docking and binding energy score than the reference (XAV939) molecule. Further, post-processing analysis by PCA and FEL studies also concluded that these hit molecules strongly bind to the TNKS1 protein. In essence, the inhibitory activity of these molecule was validated across 77 colorectal cancer cell lines by employing a deep neural network algorithm. Taken together, our study uncovers natural compounds obovaten and duartin as possible drug candidates for the treatment of cancer through TNKS1 inhibition.