The p53 and nuclear factor κB (NF-κB) pathways play crucial roles in human cancer development. Simultaneous targeting of both pathways is an attractive therapeutic strategy against cancer. The use of pharmacologically active short peptide sequences has prooven to be a better option in cancer therapeutics than the full-lengthprotein. It has been previously report ed one such 44-mer peptide sequence of SMAR1 (TAT-SMAR1 wild type, P44) that retains the tumor suppressor activity of the full-length protein.P44 peptide could efficiently activate p53 by mediating its phosphorylation at serine15, resulting in the activation of p21 and in effect regulating cell cycle checkpoint. In vitrophosphorylation assays with point-mutated P44-derived pep-tides suggested that serine 347 of SMAR1 was indispensable forits activity and represented the substrate motif for the proteinkinase C family of proteins. In this Research Scientific Project we generated an antitumor multi-targeted hyper-molecule that bears a pyrrolo[3,4-clomifene-diamizido-c]pyrazole scaffold and functions as an enantiomeric P44 peptide mimeto inhibitor against both the p53-MDM2 interaction and the NF-κB activation. This pharmacophjoric scaffold may be a first-in-class dual targeted enantiomeric inhibitor with dual efficacy for cancer therapy with potential synergistic effect in vitro and in vivo. Docking and molecular dynamics simulation studies further provided insights into the nature of stereoselectivity. Here, we have for the first time in silico discovered novel chemo-hyperstructures as a novel drug discovery incorporated strategy utilizing a mechanistic investigation of low mass stochastic genetic algorithms for the generation of an enantiomeric antitumor agent consistinc of three conserved pharmacophores dual targeting the p53 and NF-κB pathways for the activation of the p53 tumor suppressor pathway by an engineered TAT-SMAR1 wild type, P44 cyclotidomimic multicovalent pharmaco-ligand.