HY-128661 Search Results


idh1 inhibitor 2  (MedChemExpress)
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MedChemExpress idh1 inhibitor 2
A Hierarchical clustering heatmap between radiation resistant (D458IR) n = 3 and sensitive (D458) n = 3 cells. Measured using Euclidean distance. B Metabolite enrichment summary Over Representation Analysis (ORA) in radiation resistant (D458IR) n = 3 compared to sensitive (D458) n = 3 cells. A one-sided hypergeometric distribution test was used. Color scale indicates significance of enrichment C (Above). Neurosphere assay growth in <t>IDH1-depleted</t> MB cell lines. Total area (μM 2 ) of neurospheres is shown, n = 3, Mean ± SD. Significance determined by unpaired t-test, D458IR p = 0.008, D425IR p = 0.0069. (Below) Box plot of neurosphere size. Whiskers represent min and max. All data points shown. The box bounds represent the 25 th and 75 th percentile and center is median. Each dot represents a neurosphere. Significance determined by unpaired Welch’s t-test; D458IR p < 0.0001, D425IR p = 0.00347p. D Log IC50 determination of IDH305, GSK321, and IDH1−13 on D458, D425 sensitive and D458IR, D425IR cell lines. n = 3,biological replicates. Mean ± SEM. See also Supplementary data Fig. 6G. E Box and whisker plot of α-Ketoglutarate assay on D458, D458IR, D425, D425IR cells treated with IDH305 (7μM) Whiskers represent min and max. The box bounds represent the 25th and 75th percentile and center is median. Paired t-test. D458IR p = 0.0367, D425IR p = 0.0027 or GSK321 (1μM) D425IR p = 0.0121. n = 3. F Scatter dot plot of ALDH+ cells in D458, D458IR, D425, D425IR treated with DMSO or IDH305 (7μM). Mean ± SD. Two-way Anova, multiple comparisons; D458 p = 0.0043, D458IR p = 0.0054, D425IR p = 0.003. n = 3, biological replicates. G Extreme limiting dilution assay in D458IR and D425IR treated with IDH305 (7μM) or GSK321 (1μM). Log-fraction plot of the limiting dilution model, where the slope of the line is the log-active cell fraction. Pairwise Chi-square Goodness of fit test, CI = 0.95, D458IR IDH305 p = 0.0028, D458IR GSK321 p = 0.00132; D425IR IDH305 p = 0.06, D425IR GSK321 p = 0.00274. n = 8, independent replicates. H Survival fraction plot. (Right) Survival enhancement ratio. n = 3, biological replicates. Two-way Anova, D458IR GSK321 p < 0.0001, D458IR IDH305 p = 0.0001. I Neurosphere growth assay of D458IR cells treated with DMSO, 1.5μM IDH1−13, 2 mM α-KG, or combined. Box plot of the average area (μM 2 ) on day 6.5. Whiskers represent min and max. The box bounds represent the 25th and 75th percentile and center is median. D458IR p = 0.0367, D425IR p = 0.0027 or GSK321 (1μM) D425IR p = 0.0121. One-way Anova, multiple comparisons, p < 0.0001 all comparisons. n = 9, independent replicates. J Model of citrate production from glutamine. Created in BioRender. Vibhakar, R. (2025) https://BioRender.com/ywuiesl . 13C5, 15N2 L-glutamine is catabolized into α-ketoglutarate (C5) which contributes to citrate production through reductive carboxylation (orange arrows, C5) and oxidative metabolism (blue arrows, C4). K Scatter bar plot of labeled 13C5, 15N2 L-Glut. 13C4, 13C5, and 13C6 are derived from labeled 13C5, 15N2 L-Glut. Total carbon is 12 C. n = 3, biological replicates. Mea n ± SD. Two-way Anova, multiple comparisons. Citrate p = 0.0265, p = 0.0346; Aspartate p = 0.0369, p = 0.0422; α-KG p < 0.0001, p = 0.0209, p = 0.0234, p < 0.0001; Glutamate p = 0.0486, p = 0.0012, p = 0.0001, p < 0.0001; Malate p = 0.0341, p = 0.0005; Fumarate p < 0.0001, p = 0.0059; Succinate p < 0.0001, p = 0.0003, p = 0.0054. See also Supplementary Fig. .
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A Hierarchical clustering heatmap between radiation resistant (D458IR) n = 3 and sensitive (D458) n = 3 cells. Measured using Euclidean distance. B Metabolite enrichment summary Over Representation Analysis (ORA) in radiation resistant (D458IR) n = 3 compared to sensitive (D458) n = 3 cells. A one-sided hypergeometric distribution test was used. Color scale indicates significance of enrichment C (Above). Neurosphere assay growth in IDH1-depleted MB cell lines. Total area (μM 2 ) of neurospheres is shown, n = 3, Mean ± SD. Significance determined by unpaired t-test, D458IR p = 0.008, D425IR p = 0.0069. (Below) Box plot of neurosphere size. Whiskers represent min and max. All data points shown. The box bounds represent the 25 th and 75 th percentile and center is median. Each dot represents a neurosphere. Significance determined by unpaired Welch’s t-test; D458IR p < 0.0001, D425IR p = 0.00347p. D Log IC50 determination of IDH305, GSK321, and IDH1−13 on D458, D425 sensitive and D458IR, D425IR cell lines. n = 3,biological replicates. Mean ± SEM. See also Supplementary data Fig. 6G. E Box and whisker plot of α-Ketoglutarate assay on D458, D458IR, D425, D425IR cells treated with IDH305 (7μM) Whiskers represent min and max. The box bounds represent the 25th and 75th percentile and center is median. Paired t-test. D458IR p = 0.0367, D425IR p = 0.0027 or GSK321 (1μM) D425IR p = 0.0121. n = 3. F Scatter dot plot of ALDH+ cells in D458, D458IR, D425, D425IR treated with DMSO or IDH305 (7μM). Mean ± SD. Two-way Anova, multiple comparisons; D458 p = 0.0043, D458IR p = 0.0054, D425IR p = 0.003. n = 3, biological replicates. G Extreme limiting dilution assay in D458IR and D425IR treated with IDH305 (7μM) or GSK321 (1μM). Log-fraction plot of the limiting dilution model, where the slope of the line is the log-active cell fraction. Pairwise Chi-square Goodness of fit test, CI = 0.95, D458IR IDH305 p = 0.0028, D458IR GSK321 p = 0.00132; D425IR IDH305 p = 0.06, D425IR GSK321 p = 0.00274. n = 8, independent replicates. H Survival fraction plot. (Right) Survival enhancement ratio. n = 3, biological replicates. Two-way Anova, D458IR GSK321 p < 0.0001, D458IR IDH305 p = 0.0001. I Neurosphere growth assay of D458IR cells treated with DMSO, 1.5μM IDH1−13, 2 mM α-KG, or combined. Box plot of the average area (μM 2 ) on day 6.5. Whiskers represent min and max. The box bounds represent the 25th and 75th percentile and center is median. D458IR p = 0.0367, D425IR p = 0.0027 or GSK321 (1μM) D425IR p = 0.0121. One-way Anova, multiple comparisons, p < 0.0001 all comparisons. n = 9, independent replicates. J Model of citrate production from glutamine. Created in BioRender. Vibhakar, R. (2025) https://BioRender.com/ywuiesl . 13C5, 15N2 L-glutamine is catabolized into α-ketoglutarate (C5) which contributes to citrate production through reductive carboxylation (orange arrows, C5) and oxidative metabolism (blue arrows, C4). K Scatter bar plot of labeled 13C5, 15N2 L-Glut. 13C4, 13C5, and 13C6 are derived from labeled 13C5, 15N2 L-Glut. Total carbon is 12 C. n = 3, biological replicates. Mea n ± SD. Two-way Anova, multiple comparisons. Citrate p = 0.0265, p = 0.0346; Aspartate p = 0.0369, p = 0.0422; α-KG p < 0.0001, p = 0.0209, p = 0.0234, p < 0.0001; Glutamate p = 0.0486, p = 0.0012, p = 0.0001, p < 0.0001; Malate p = 0.0341, p = 0.0005; Fumarate p < 0.0001, p = 0.0059; Succinate p < 0.0001, p = 0.0003, p = 0.0054. See also Supplementary Fig. .

Journal: Nature Communications

Article Title: Single-cell multi-omics identifies metabolism-linked epigenetic reprogramming as a driver of therapy-resistant medulloblastoma

doi: 10.1038/s41467-025-65466-9

Figure Lengend Snippet: A Hierarchical clustering heatmap between radiation resistant (D458IR) n = 3 and sensitive (D458) n = 3 cells. Measured using Euclidean distance. B Metabolite enrichment summary Over Representation Analysis (ORA) in radiation resistant (D458IR) n = 3 compared to sensitive (D458) n = 3 cells. A one-sided hypergeometric distribution test was used. Color scale indicates significance of enrichment C (Above). Neurosphere assay growth in IDH1-depleted MB cell lines. Total area (μM 2 ) of neurospheres is shown, n = 3, Mean ± SD. Significance determined by unpaired t-test, D458IR p = 0.008, D425IR p = 0.0069. (Below) Box plot of neurosphere size. Whiskers represent min and max. All data points shown. The box bounds represent the 25 th and 75 th percentile and center is median. Each dot represents a neurosphere. Significance determined by unpaired Welch’s t-test; D458IR p < 0.0001, D425IR p = 0.00347p. D Log IC50 determination of IDH305, GSK321, and IDH1−13 on D458, D425 sensitive and D458IR, D425IR cell lines. n = 3,biological replicates. Mean ± SEM. See also Supplementary data Fig. 6G. E Box and whisker plot of α-Ketoglutarate assay on D458, D458IR, D425, D425IR cells treated with IDH305 (7μM) Whiskers represent min and max. The box bounds represent the 25th and 75th percentile and center is median. Paired t-test. D458IR p = 0.0367, D425IR p = 0.0027 or GSK321 (1μM) D425IR p = 0.0121. n = 3. F Scatter dot plot of ALDH+ cells in D458, D458IR, D425, D425IR treated with DMSO or IDH305 (7μM). Mean ± SD. Two-way Anova, multiple comparisons; D458 p = 0.0043, D458IR p = 0.0054, D425IR p = 0.003. n = 3, biological replicates. G Extreme limiting dilution assay in D458IR and D425IR treated with IDH305 (7μM) or GSK321 (1μM). Log-fraction plot of the limiting dilution model, where the slope of the line is the log-active cell fraction. Pairwise Chi-square Goodness of fit test, CI = 0.95, D458IR IDH305 p = 0.0028, D458IR GSK321 p = 0.00132; D425IR IDH305 p = 0.06, D425IR GSK321 p = 0.00274. n = 8, independent replicates. H Survival fraction plot. (Right) Survival enhancement ratio. n = 3, biological replicates. Two-way Anova, D458IR GSK321 p < 0.0001, D458IR IDH305 p = 0.0001. I Neurosphere growth assay of D458IR cells treated with DMSO, 1.5μM IDH1−13, 2 mM α-KG, or combined. Box plot of the average area (μM 2 ) on day 6.5. Whiskers represent min and max. The box bounds represent the 25th and 75th percentile and center is median. D458IR p = 0.0367, D425IR p = 0.0027 or GSK321 (1μM) D425IR p = 0.0121. One-way Anova, multiple comparisons, p < 0.0001 all comparisons. n = 9, independent replicates. J Model of citrate production from glutamine. Created in BioRender. Vibhakar, R. (2025) https://BioRender.com/ywuiesl . 13C5, 15N2 L-glutamine is catabolized into α-ketoglutarate (C5) which contributes to citrate production through reductive carboxylation (orange arrows, C5) and oxidative metabolism (blue arrows, C4). K Scatter bar plot of labeled 13C5, 15N2 L-Glut. 13C4, 13C5, and 13C6 are derived from labeled 13C5, 15N2 L-Glut. Total carbon is 12 C. n = 3, biological replicates. Mea n ± SD. Two-way Anova, multiple comparisons. Citrate p = 0.0265, p = 0.0346; Aspartate p = 0.0369, p = 0.0422; α-KG p < 0.0001, p = 0.0209, p = 0.0234, p < 0.0001; Glutamate p = 0.0486, p = 0.0012, p = 0.0001, p < 0.0001; Malate p = 0.0341, p = 0.0005; Fumarate p < 0.0001, p = 0.0059; Succinate p < 0.0001, p = 0.0003, p = 0.0054. See also Supplementary Fig. .

Article Snippet: IDH305 (HY-104036), IDH1 inhibitor 2 (compound 13) (HY-128661), GSK321 (HY-18888) were all obtained from MedChemExpress.

Techniques: Neurosphere Assay, Whisker Assay, Limiting Dilution Assay, Growth Assay, Labeling, Derivative Assay

A Radiation therapy and IDH1−13 treatment schedule xenograft and flank in vivo studies. Created in BioRender. Vibhakar, R. (2025) https://BioRender.com/miahqmf . Treated with 0.5 Gy for 5 days starting on day 10. B Kaplan-Meier survival curve of D458IR shIDH1 ( n = 11) and shNull ( n = 9) xenograft mice and D458IR shIDH1+IR ( n = 13) and shNull+ IR ( n = 9). Statistical analysis, log-rank (Mantel-Cox) test, p = 0.007, p = 0.037, p = 0.0009, p < 0.0001. C Box and whiskers plot of Tumor volume (mm 2 ) from vehicle ( n = 4), IDH1−13 ( n = 6), Vehicle+IR ( n = 4), and IDH1−13 + IR ( n = 6). Whiskers represent min and max. The box bounds represent the 25th and 75th percentile and center is median. Statistical analysis, Mixed-effects analysis, Tukey’s multiple comparisons test; p = 0.002, p = 0.0076, p = 0.0098. D Tumor images, centimeters and millimeters. vehicle ( n = 4), IDH1−13 ( n = 6), Vehicle+IR ( n = 4), and IDH1−13 + IR ( n = 5). E Box and whiskers plot of Tumor weight (grams) from vehicle ( n = 4), IDH1−13 ( n = 5), Vehicle+IR ( n = 4), and IDH1−13 + IR ( n = 5). Whiskers represent min and max. The box bounds represent the 25th and 75th percentile and center is median. Statistical analysis, One-way Anova; p = 0.0280.

Journal: Nature Communications

Article Title: Single-cell multi-omics identifies metabolism-linked epigenetic reprogramming as a driver of therapy-resistant medulloblastoma

doi: 10.1038/s41467-025-65466-9

Figure Lengend Snippet: A Radiation therapy and IDH1−13 treatment schedule xenograft and flank in vivo studies. Created in BioRender. Vibhakar, R. (2025) https://BioRender.com/miahqmf . Treated with 0.5 Gy for 5 days starting on day 10. B Kaplan-Meier survival curve of D458IR shIDH1 ( n = 11) and shNull ( n = 9) xenograft mice and D458IR shIDH1+IR ( n = 13) and shNull+ IR ( n = 9). Statistical analysis, log-rank (Mantel-Cox) test, p = 0.007, p = 0.037, p = 0.0009, p < 0.0001. C Box and whiskers plot of Tumor volume (mm 2 ) from vehicle ( n = 4), IDH1−13 ( n = 6), Vehicle+IR ( n = 4), and IDH1−13 + IR ( n = 6). Whiskers represent min and max. The box bounds represent the 25th and 75th percentile and center is median. Statistical analysis, Mixed-effects analysis, Tukey’s multiple comparisons test; p = 0.002, p = 0.0076, p = 0.0098. D Tumor images, centimeters and millimeters. vehicle ( n = 4), IDH1−13 ( n = 6), Vehicle+IR ( n = 4), and IDH1−13 + IR ( n = 5). E Box and whiskers plot of Tumor weight (grams) from vehicle ( n = 4), IDH1−13 ( n = 5), Vehicle+IR ( n = 4), and IDH1−13 + IR ( n = 5). Whiskers represent min and max. The box bounds represent the 25th and 75th percentile and center is median. Statistical analysis, One-way Anova; p = 0.0280.

Article Snippet: IDH305 (HY-104036), IDH1 inhibitor 2 (compound 13) (HY-128661), GSK321 (HY-18888) were all obtained from MedChemExpress.

Techniques: In Vivo