Fig. 3: MTHFD2 inhibitors display high potency and cancer selectivity in AML models.
a, Evaluation of the MTHFD2 inhibitors TH7299, TH9028 and TH9619 compared with MTX, AraC and ATRA on cell viability at 96 h of treatment across a panel of leukemia cell lines. LCLs LCL-534 and LCL-889 established from healthy primary B cells are shown as nontumorigenic controls (Extended Data Fig. 4). Data are shown as means (n = 2 independent cell cultures). A representative of two independent experiments is shown. b, Annexin-V/PI flow cytometry analysis of apoptosis in HL-60 and LCL-889 cells on TH7299, TH9028 or TH9619 for 96 h (Extended Data Fig. 4). Approximately 20,000 events were analyzed per condition. The quantification of double-positive (annexin-V positive and PI positive) late apoptotic populations is shown as pooled means ± s.d. from two independent experiments performed in duplicate. *P = 0.0168, ****P < 0.0001; two-way ANOVA (FTH7299 = 650.9, FTH9028 = 80.27, FTH9619 = 246, d.f. = 1). c, Viability dose–response curves of CCD 841 normal colon epithelial cells compared with HL-60 cells on treatment with MTHFD2 inhibitors (TH7299, TH9028, TH9619, LY345899 and DS18561882), ATR inhibitors (VE-821, VE-822), 5-FU or KRASi (BAY-293) evaluated after 96 h (Extended Data Fig. 4). Data are shown as means (n = 2). A representative of two independent experiments is shown. d, Cell viability dose–response curves of primary CD34+ bone marrow cells from healthy donors compared with HL-60 cells on treatment with TH7299, TH9028 or DMSO, evaluated after 72 h. Data from one representative experiment are displayed as means (n = 2 independent cell cultures).
