Fig. 5: Indisulam modulates the metabolome and glucose utilisation.

a KELLY Parental (PAR), DCAF15^WT or DCAF15^KO dosed with vehicle control (VC, 0.1% DMSO) or 10 µM indisulam for 24 h and intracellular metabolites analysed by HILIC LC–MS/MS. Heatmap showing hierarchal clustering of significantly altered metabolites (p-adj < 0.001, Kruskal–Wallis test, MetaboAnalyst). Data are an average of four technical replicates of n = 2 independent experiments. b Schematic representation of enrichment of ¹³C derived from ¹³C₆-glucose into TCA cycle intermediates detected by GC-MS. c–h KELLY PARENTAL (PAR), DCAF15^WT or DCAF15^KO cells were exposed to indisulam in the presence of 5.6 mM ¹³C₆-glucose for 24 h. Fraction of carbons labelled from ¹³C₆-Glucose in Citrate (c), Alanine (d) and Pyruvate (e). M + n: a metabolite with n carbon atoms labelled with ¹³C. Data are mean of n = 3 independent experiments, n = 2 for Alanine. Changes in M + 2 labelled Citrate (f), M + 3 labelled Alanine (g) and M + 3 labelled Pyruvate (h) following indisulam exposure. (n = 3 independent experiments, n = 2 for Alanine). Data are presented as mean values ± SEM (f–h). Statistical significance in f and h was determined by a two-sided unpaired t-test. Source data is provided as a Source Data File. UTP uridine triphosphate, ITP inosine triphosphate, ATP adenosine triphosphate, dGTP deoxyguanosine triphosphate, SAM S-Adenosyl methionine, dCTP deoxycytidine triphosphate, dATP deoxyadenosine triphosphate, CTP cytidine triphosphate, IDP inosine diphosphate, DHAP dihydroxyacetone phosphate, UMP uridine monophosphate, GDP guanosine diphosphate, IMP inosine monophosphate, AMP adenosine monophosphate.