Table 2 Sex-aware drug repurposing examples

Data Mining

Drug Central [149]

Database

Drug Database compilation using FDA, EMA, and PMDA; information includes active ingredients, MOA’s, indivations, pharmacological actions, regulatory data, chemical structure, and adverse drug events separated by sex to help correct for sex-bias

AwareDX [7]

Study/Analysis

Pharmacovigilance algorithm that predicts sex-bias adverse events from FAERS data and found 20,817 sex-specific drug risks

“Sex differences in pharmacokinetics predict adverse drug reactions in women” ([14])

Study/Analysis

Pharmacokinetic differences by sex are linked to sex-specific adverse drug reactions using data procured from ISI Web of Science and PubMed

Molecular Association

“Gender differences in the effects of cardiovascular drugs” [18]

Study/Analysis

Sex influences on pharmacokinetics, pharmacodynamics, and other physiological factors are reviewed for cardiovascular drug response

“Brd4-bound enhancers drive cell-intrinsic sex differences in glioblastoma” [150]

Study/Analysis

Sex-specific epigenetic signatures are identified in GBM mouse astrocytes and human glioblastoma stem cells

“Sex-Dependent Gene Co-Expression in the Human Body” [25]

Study/Analysis

Across-tissue RNAseq analysis finds co-expression to be highly sex-dependent

Networks

“Population-scale identification of differential adverse events before and during a pandemic” [9]

Study/Analysis

Sex-specific desparities are presented in network analysis of adverse drug events before and during COVID-19 pandemic

“Gene regulatory network analysis identifies sex-linked differences in colon cancer drug metabolism” [17]

Analysis using PANDA and LIONESS

Molecular differences investigated using sex-specific networks to uncover role in metabolism of drugs in colon cancer

“Sex Differences in Gene Expression and Regulatory Networks across 29 Human Tissues” [151]

Analysis using LIONESS

Sex biases are found in patient-specific networks in every tissue and by disease

“Detecting phenotype-driven transitions in regulatory network structure” [152]

Analysis using ALPACA

Sexual dimorphism are investigated in human breast tissue gene expression networks

Ligand-Binding Prediction

“3D pharmacophoric similarity improves multi adverse drug event identification in pharmacovigilance” [165]

Study/Analysis

Pharmaceutical 3D structure similarity predictions are combined with adverse drug events as a method that may be applied for comparing safety by sex-aware reporting

Experimental

“Sexual differentiation of central vasopressin and vasotocin systems in vertebrates: different mechanisms, similar endpoints” [153]

Study/Analysis

Rat model is used in comparison with human model to compare sex-bias of common neuropsychiatric drug targets