Potency and cell-line selectivity did not go hand-in-hand across all targeted cancer cell lines. In fact, they would correlate with specific physicochemical properties of mACPs across three clusters made of cancer cell lines. In the first cluster, grouping HeLa S3 (cervix), CCRF-CEM (blood) and SW-480 (colon), more hydrophobicity led to more potent mACPs, whereas a greater net charge diminished their cell-line selectivity, as illustrated by selective HAL-1 and LL-III homologues (sequence motif Figure ) and non-selective Macropin-1 examples -Figure . These findings corroborated with previous structure-activity relationships studies of α-helical cationic peptide P and temporin-1CEa , where hydrophobicity led to stronger anticancer activities against multiple cancer cell lines (cervix: HeLa, melanoma: A375, B16, lung: A549 and breast: MCF-7, MDA-MB-231, Bcap-37). Because the pIC50 values were in the same order of magnitude across cell lines, both studies did not conduct the rationale design of selective peptide analogues. In the second cluster made of cancer cell lines NCI-H157 and A549 (lung), PC-3 (prostate), U251-MG (brain) and HL-60 (blood), the design of more potent mACPs was associated with an increase in positively charged residues. Harris and co-workers have previously mentioned the important role that both lysine and arginine side chains play in interacting with membranes via a "snorkelling" mechanism. The cell-line selective mACPs like dermaseptins contained successive small residues, e.g. alanine, glycine (sequence motif Figure ), whereas non-selective examples (e.g. TsAP-1 and TsAP-2) presented higher levels of hydrophobicity -Figure . The α-helical-forming propensity and amphipathic nature of alanine-rich peptides have long been associated with their ability to penetrate microbial and cancer cell membranes . Dermaseptins are a welldocumented family of antimicrobial and anticancer peptides derived from frog skins . In 2017, Dos Santos and co-workers revealed the role of cell surface glycosaminoglycans in the anticancer mechanism of action of dermaseptin-B2 , which might explain the cell-line selectivity of this peptide and other members of dermaseptin family toward certain cell lines. Finally, the third and last cluster included blood cancer cell lines Jurkat E6-1 and K562 as well as breast cancer cell line MDA-MB-361. In that cluster, we only reported cell-line non-selective mACPs from three populated peptide families; P18, CRAMP18 and BP100 homologues (sequence motif Figure ). Their potency was partly linked to their hydrophobicity, supporting previous observations against multiple cancer cell lines .