In cancer cells, overexpression of pro-survival proteins can block proapoptotic signalling by sequestering the BH3-only proteins.6 Thus, inhibition of pro-survival proteins has emerged as a promising approach for cancer treatment e.g. the BCL-2 inhibitor, venetoclax (AT-199).8 In this work, we used the Harakiri (HRK) BH3 domain as a template to design constrained peptidomimetic ligands for the BCL-xL protein. This evidence concerns the gene BCL2 and cancer.