Repurposing of Nemiralisib as a Potential CDK4 Inhibitor for Breast Cancer Treatment: A Ligand-Based Virtual Screening and Docking Study

As part of the drug repurposing efforts, a pliable PI3K inhibitor Nemiralisib that was developed for use in respiratory diseases was studied for her potential use as a new CDK4 inhibitor in the treatment of breast cancer. Utilization of ligand based virtual screening and molecular docking studies further revealed an appreciable binding affinity of Nemiralisib to CDK4 with a docking score of – 11.1 which is markedly similar to that of an already established CDK4/6 inhibitor, Abemaciclib (-11.5). From structural studies, it was clear that Nemiralisib binds to the CDK4 binding pocket using several residues such as GLU11, ILE12 and ASP97 in a way similar to how Abemaciclib does. Moreover, additional synergy prediction studies using the PISCEScsm platform anticipated the effects of the combination, especially in breast cancer of Nemiralisib with Fulvestrant and Tamoxifen to be more than additive. All these data support the idea that Nemiralisib may be a useful drug to add to the treatment of hormone receptor-positive breast cancer and improve currently existing therapies. This study opens doors of using Nemiralisib in the field of oncology, with an encouraging avenue of treatment for breast cancer patients.