Figure 3.
MB1-47 depletes TCA intermediates and NTPs in T-ALL cells. (A) Relative glucose abundance in media from DND41 cells cultured in the presence or absence of MB1-47 (mean ± SD; n = 3). (B) Relative lactate abundance in media from DND41 cells cultured in the presence or absence of MB1-47 (mean ± SD; n = 3). (C) Significantly altered metabolites after MB1-47 exposure, ranked by P value (−log10 transformed). (D) Intracellular ratio of NAD+/NADH (left) and pyruvate/lactate (right) in DND41 cells cultured in the presence or absence of MB1-47 (n = 6, from 2 independent replicates; bar graphs represent mean ± SD). (E) Relative abundance of indicated TCA intermediates in DND41 cells cultured in the presence or absence of MB1-47 (n = 9, from 3 independent experiments). (F) Heat map showing differential intracellular amino acid abundances (log2) after MB-47 treatment, relative to DMSO-treated (control) cells. (G) Relative abundance of aspartate in DND41 cells cultured in the presence or absence of MB1-47 (n = 9, from 3 independent experiments; mean ± SD). (H) Heat map showing differential intracellular nucleotide abundance (log2) after exposure to MB1-47, relative to DMSO-treated (control) cells. (I) Relative abundance of indicated UDP sugars in DND41 cells cultured in the presence or absence of MB1-47. All measurements were determined after MB1-47 (4 μM) treatment of 24 hours and are relative to DMSO-treated (control) cells. (J) Immunoblot analyses of AMPK, ACC, and 4E-BP1 in DND41 cells treated with DMSO or MB1-47 (4 μM) for either 2 or 4 hours. Statistical significance (P) was determined by using the 2-tailed Student t test. *P < .05; ***P < .005.

MB1-47 depletes TCA intermediates and NTPs in T-ALL cells. (A) Relative glucose abundance in media from DND41 cells cultured in the presence or absence of MB1-47 (mean ± SD; n = 3). (B) Relative lactate abundance in media from DND41 cells cultured in the presence or absence of MB1-47 (mean ± SD; n = 3). (C) Significantly altered metabolites after MB1-47 exposure, ranked by P value (−log10 transformed). (D) Intracellular ratio of NAD+/NADH (left) and pyruvate/lactate (right) in DND41 cells cultured in the presence or absence of MB1-47 (n = 6, from 2 independent replicates; bar graphs represent mean ± SD). (E) Relative abundance of indicated TCA intermediates in DND41 cells cultured in the presence or absence of MB1-47 (n = 9, from 3 independent experiments). (F) Heat map showing differential intracellular amino acid abundances (log2) after MB-47 treatment, relative to DMSO-treated (control) cells. (G) Relative abundance of aspartate in DND41 cells cultured in the presence or absence of MB1-47 (n = 9, from 3 independent experiments; mean ± SD). (H) Heat map showing differential intracellular nucleotide abundance (log2) after exposure to MB1-47, relative to DMSO-treated (control) cells. (I) Relative abundance of indicated UDP sugars in DND41 cells cultured in the presence or absence of MB1-47. All measurements were determined after MB1-47 (4 μM) treatment of 24 hours and are relative to DMSO-treated (control) cells. (J) Immunoblot analyses of AMPK, ACC, and 4E-BP1 in DND41 cells treated with DMSO or MB1-47 (4 μM) for either 2 or 4 hours. Statistical significance (P) was determined by using the 2-tailed Student t test. *P < .05; ***P < .005.

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