(A) Steady-state quantification of the indicated metabolites in BT054 GSCs treated with 10 nM BAY 2402234, 5 μM lometrexol, or DMSO (n = 8 per condition).
(B) Pathways targeted by BAY 2402234 (BAY) and lometrexol (Lom).
(C) 15N stable isotope tracing assays in BT054 and TS516 GSC lines (n = 3).
(D) Select pathways using intermediates derived from de novo pyrimidine nucleotide synthesis.
(E and F) Volcano plots of metabolites in HOG-EV (E) or HOG-R132H (F) cells treated with 10 nM BAY 2402234 relative to DMSO (n = 4).
(G) Ratio of pyrimidine (dTTP, dCTP) to purine (dATP) deoxynucleotide triphosphate (dNTP) pools in cells shown in (E and F). For all panels, data are means ± SEM; *p < 0.05, ***p < 0.001. n.s., not significant. Two-tailed p values were determined by unpaired t test.