Fig. 5: Drug compound selection and validation of drug efficacy using clinical samples.

a Network diagram of HGSC targets (CDKs and EHMT2) and targeting compounds (STITCH score >0.95). Edge thickness represents combined STITCH confidence score. Round nodes and diamond nodes represent compounds that have undergone some phase of clinical trials and have not undergone clinical trials, respectively. Compound node colours represent compound mechanism of action (MOA). Factor node outline colour indicates the number of the expressed complexes which the factor is a component of. Red and green highlight circles indicate CDK and EHMT-related protein groups respectively. b Heatmap representing the effect of drug compounds on patient-derived clinical samples treated for 72 h. Each 4 rows of the heatmap represent the top concentrations used to derive IC₅₀ values (10 μM, 1 μM, 100 nM and 10 nM). Heatmap values were calculated using relative viability compared to the vehicle control (DMSO). Red colour indicates low viability following treatment. c Table displaying calculated best fit IC₅₀ values after 72 h of treatment with varying concentrations (10 pM-10 μM) of displayed drug compounds. DMSO was used as vehicle control and staurosporine was used as positive control (+). d Flow cytometry cell cycle analyses of CAOV3 and OVCAR-3 cells treated with selected compounds for 24 h. Bar chart error represents coefficients of variation (cv). Blue peaks represent cells in G0/G1, while green peaks represent cells in G2/M phase. The area depicted as yellow represents cells in the S phase. e Flow cytometry apoptosis analysis of CAOV3 and OVCAR-3 cells treated with selected compounds for 24 h. Cells were stained with Propidium iodide and Annexin V-FITC, rendering 4 populations: viable (−, −), early apoptotic (−,+), late apoptotic (+, +) and dead (+, −), three of which are highlighted in the panels. Graphs display cell densities, whereby red, green and blue colours indicate high, medium and low cell densities, respectively.