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val-083 (Adooq Bioscience LLC)

Name: val-083
Brand: Adooq Bioscience LLC
Rating: 90 (1 reviews)

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Adooq Bioscience LLC val-083

Val 083, supplied by Adooq Bioscience LLC, used in various techniques. Bioz Stars score: 90/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
https://www.bioz.com/result/val-083/product/Adooq Bioscience LLC
Average 90 stars, based on 1 article reviews

val-083 - by Bioz Stars, 2026-02

90/100 stars

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1) Product Images from "Dianhydrogalactitol Overcomes Multiple Temozolomide Resistance Mechanisms in Glioblastoma"

Article Title: Dianhydrogalactitol Overcomes Multiple Temozolomide Resistance Mechanisms in Glioblastoma

Journal: Molecular cancer therapeutics

doi: 10.1158/1535-7163.MCT-20-0319

Figure Legend Snippet: Val-083 cytotoxicity is exerted independently of MMR or MGMT expression. A, Viability of parental U-251 MG, T98G, U-87 MG, LN-18, and SF268 cell lines upon exposure to different concentrations of Val-083 measured by MTT. Values are represented as percentage of cell viability compared with DMSO control. B, Cell-cycle profile of U-251 MG or T98G cells treated with different doses of TMZ or Val-083 for 48 hours. C, Competition assay of U-251 MG cells expressing shRNAs targeting MSH6 (shMSH6.3908), PMS2 (shPMS2.946), and MSH2 (shMSH2.357) after treatment with TMZ or VAL-083. The plotted value is the fold enrichment of the shRNA-expressing cells (eGFP+) compared with the control cells (mCherry+) and normalized to the DMSO control. Statistical test: Two-way ANOVA (P values: *P < 0.05, **P < 0.01, compared with DMSO treated). D, CFA of U-251 MG cells expressing control shRNA or shMSH6 after treatment with TMZ or Val-083 for 9 days. E, Cell-cycle profile of U-251 MG cells expressing control shRNA (shRen.660) or shMSH6.3908 after treatment with TMZ or Val-083 for 48 hours. F, Quantification of mean γH2AX fluorescence in nuclei of cells treated with vehicle, TMZ, or Val-083 for 48 hours. Values are normalized to the DMSO control, and fold increase in H2AX signal is plotted. Statistical test: Two-way ANOVA (P values: ***, P < 0.001; ****, P < 0.0001, compared with DMSO treated).

Techniques Used: Expressing, Competitive Binding Assay, shRNA, Fluorescence

Figure Legend Snippet: TMZ and Val-083 combination treatment show synergistic cytotoxic effect. A, Table showing the percentage of cell viability (as compared with DMSO, top number in each cell) and SD (bottom number). B, Plot of synergy score calculated with the HSA method of U-251 MG cells treated with different doses of TMZ and Val-083. C, Table showing the maximum synergy scores of different adherent cell lines (U-251 MG, T98G, U-87 MG, SF268, LN-18) and tumorspheres grown in suspension (H543, H516, H676), as well as the doses of TMZ and Val-083, which rendered said score. MGMT expression is also indicated. D, CFA of U-251 MG cells incubated with low doses of TMZ, Val-083, or the combination for 9 days. E, Cell-cycle profile of U-251 MG cells incubated for 48 hours with TMZ, Val-083, or the combination of both. F, Representative pictures of γH2AX staining of U-251 MG cells treated for 48 hours with DMSO, TMZ, Val-083, or the combination of the last two. G, Quantification of γH2AX signal intensity in nuclei of U-251 MG cells treated for 48 hours with TMZ, Val-083, or the combination of both. Statistical test (P values: ***, P < 0.001). H, CFA of T98G cells incubated with high and low doses of TMZ, Val-083, or the combination for 9 days. I, Quantification of γH2AX signal intensity in nuclei of T98G cells treated for 48 hours with TMZ, Val-083, or the combination of both. Statistical test: t test (P values: *, P < 0.05; ***, P < 0.001).

Techniques Used: Expressing, Incubation, Staining

Treatment with combination of TMZ and Val-083 increases survival in mice. A, Quantification of the ratio of luminescence emission by U251-MG in ex vivo-treated brain slices after 7 days as compared with the initial. Plots represent the fold change compared with the DMSO control. Statistical test: t test (P values: *, P < 0.05; **, P < 0.01; ***, P < 0.001; ns, nonsignficant); P values on top of the boxes are comparison over the DMSO control. B, Kaplan–Meier curve showing the survival proportions of mice transplanted with U-251 MG cells and treated with TMZ, Val-083, or the combination of both. Log-rank P values: **, P < 0.01; ns, nonsignificant). C, Kaplan–Meier curve showing the survival proportions of mice transplanted with H676 cells and treated with TMZ, Val-083, or the combination of both. Log-rank P values: **, P < 0.01; ns, nonsignificant).

Figure Legend Snippet: Treatment with combination of TMZ and Val-083 increases survival in mice. A, Quantification of the ratio of luminescence emission by U251-MG in ex vivo-treated brain slices after 7 days as compared with the initial. Plots represent the fold change compared with the DMSO control. Statistical test: t test (P values: *, P < 0.05; **, P < 0.01; ***, P < 0.001; ns, nonsignficant); P values on top of the boxes are comparison over the DMSO control. B, Kaplan–Meier curve showing the survival proportions of mice transplanted with U-251 MG cells and treated with TMZ, Val-083, or the combination of both. Log-rank P values: **, P < 0.01; ns, nonsignificant). C, Kaplan–Meier curve showing the survival proportions of mice transplanted with H676 cells and treated with TMZ, Val-083, or the combination of both. Log-rank P values: **, P < 0.01; ns, nonsignificant).

Techniques Used: Ex Vivo

Mechanisms of action of TMZ and Val-083. Expression of MGMT effectively removes the O6-guanine methylation induced by TMZ exposure, which allows cell survival. Lack of MGMT allows the formation of mismatches in the next replication round, which leads to the generation of double DNA-strand breaks mediated by the MMR machinery. The accumulation of double-strand breaks ultimately lead to cell death. However, defects in the MMR pathway paves the way for the accumulation of unresolved mismatches, which allows cell survival and a hypermutation phenotype. In the case of Val-083, there is a formation of interstrand adducts, that are not resolved by MGMT, and lead to cytotoxicity independently of MMR status.

Figure Legend Snippet: Mechanisms of action of TMZ and Val-083. Expression of MGMT effectively removes the O6-guanine methylation induced by TMZ exposure, which allows cell survival. Lack of MGMT allows the formation of mismatches in the next replication round, which leads to the generation of double DNA-strand breaks mediated by the MMR machinery. The accumulation of double-strand breaks ultimately lead to cell death. However, defects in the MMR pathway paves the way for the accumulation of unresolved mismatches, which allows cell survival and a hypermutation phenotype. In the case of Val-083, there is a formation of interstrand adducts, that are not resolved by MGMT, and lead to cytotoxicity independently of MMR status.

Techniques Used: Expressing, Methylation

Image Search Results

Gene expression analysis of CCMA datasets reveals significantly higher ( a ) MGMT expression in H3K27-DMG cell lines compared to adult HGG and H3G34-DHG cell lines, and ( b ) significantly higher WEE1 expression in adult HGG, ATRT, H3K27-DMG and H3WT-HGG cell lines compared to non-malignant cells. Kruskal-Wallis test with Dunn’s multiple comparisons test was conducted; * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001. c , d Dose response curve of Val-083 and AZD1775 on ten DMG/HGG cell lines. e IC 50 range and median IC 50 of Val-083 and AZD1775 on responsive cell lines based on their H3 status. f Val-083 induces DNA damage and DNA repair response through ATR-mediated signaling pathway. g AZD1775 inhibits Wee1 kinase to reduce inhibitory phosphorylation of CDK1 and CDK2 and induce cell cycle checkpoint impairment.

Journal: NPJ Precision Oncology

Article Title: Dual treatment with Val-083 and AZD1775 shows potent anti-tumor activity in diffuse midline glioma models

doi: 10.1038/s41698-025-01006-4

Figure Lengend Snippet: Gene expression analysis of CCMA datasets reveals significantly higher ( a ) MGMT expression in H3K27-DMG cell lines compared to adult HGG and H3G34-DHG cell lines, and ( b ) significantly higher WEE1 expression in adult HGG, ATRT, H3K27-DMG and H3WT-HGG cell lines compared to non-malignant cells. Kruskal-Wallis test with Dunn’s multiple comparisons test was conducted; * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001. c , d Dose response curve of Val-083 and AZD1775 on ten DMG/HGG cell lines. e IC 50 range and median IC 50 of Val-083 and AZD1775 on responsive cell lines based on their H3 status. f Val-083 induces DNA damage and DNA repair response through ATR-mediated signaling pathway. g AZD1775 inhibits Wee1 kinase to reduce inhibitory phosphorylation of CDK1 and CDK2 and induce cell cycle checkpoint impairment.

Article Snippet: Val-083 (HY-16513) for in vitro testing and AZD1775 (HY-10993) were purchased from MedChemExpress, NJ, USA.

Techniques: Gene Expression, Expressing, Phospho-proteomics

Dose response curve and ZIP synergy scores reveal that Val-083 and AZD1775 combination is synergistic on ( a ) CNHDMG-762 and additive on ( b ) SF8628, ( c ) SF10693 ( d ) HSJD-DIPG-007, e CNHDMG-967 and ( f ) 7316-913. g ZIP, Bliss and Loewe synergy scores with the most synergistic area scores on the six DMG cell lines. h Western blot assay demonstrates that Val-083 and AZD1775 combination induces DNA damage (upregulated γ-H2AX), activates DNA damage response via ATR and Chk1, and reduces inhibitory phosphorylation of CDK1 and CDK2 initiated by Val-083.

Journal: NPJ Precision Oncology

Article Title: Dual treatment with Val-083 and AZD1775 shows potent anti-tumor activity in diffuse midline glioma models

doi: 10.1038/s41698-025-01006-4

Figure Lengend Snippet: Dose response curve and ZIP synergy scores reveal that Val-083 and AZD1775 combination is synergistic on ( a ) CNHDMG-762 and additive on ( b ) SF8628, ( c ) SF10693 ( d ) HSJD-DIPG-007, e CNHDMG-967 and ( f ) 7316-913. g ZIP, Bliss and Loewe synergy scores with the most synergistic area scores on the six DMG cell lines. h Western blot assay demonstrates that Val-083 and AZD1775 combination induces DNA damage (upregulated γ-H2AX), activates DNA damage response via ATR and Chk1, and reduces inhibitory phosphorylation of CDK1 and CDK2 initiated by Val-083.

Article Snippet: Val-083 (HY-16513) for in vitro testing and AZD1775 (HY-10993) were purchased from MedChemExpress, NJ, USA.

Techniques: Western Blot, Phospho-proteomics

a 24 h and 48 h cell cycle assay reveal increased cell population at S and G2/M phases which is modified with the addition of AZD1775. b 24 h and 48 h apoptosis assay reveal increased cells in the early and late apoptotic phase upon Val-083 and AZD1775 single and combination treatment. c Percentage of cell population at SubG1, G1, S and G2/M phases after 24 h of treatment with vehicle, Val-083, AZD1775 and combination drugs. d Percentage of cell population at SubG1, G1, S and G2/M phases after 48 h of treatment with vehicle, Val-083, AZD1775 and combination drugs. e Percentage of total apoptotic cells is significantly increased upon AZD1775 and combination treatment at 24- and 48 h post-treatment, while Val-083 treatment is significant only after 48 h of treatments. f Western blot analysis of cleaved PARP shows that the combination treatment significantly increases cleaved PARP activation. All data are shown as mean ± standard deviation ( n = 3). Statistically significant difference (Two-way ANOVA, Tukey’s post-hoc test) is shown as * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001 or ns (not significant).

Journal: NPJ Precision Oncology

Article Title: Dual treatment with Val-083 and AZD1775 shows potent anti-tumor activity in diffuse midline glioma models

doi: 10.1038/s41698-025-01006-4

Figure Lengend Snippet: a 24 h and 48 h cell cycle assay reveal increased cell population at S and G2/M phases which is modified with the addition of AZD1775. b 24 h and 48 h apoptosis assay reveal increased cells in the early and late apoptotic phase upon Val-083 and AZD1775 single and combination treatment. c Percentage of cell population at SubG1, G1, S and G2/M phases after 24 h of treatment with vehicle, Val-083, AZD1775 and combination drugs. d Percentage of cell population at SubG1, G1, S and G2/M phases after 48 h of treatment with vehicle, Val-083, AZD1775 and combination drugs. e Percentage of total apoptotic cells is significantly increased upon AZD1775 and combination treatment at 24- and 48 h post-treatment, while Val-083 treatment is significant only after 48 h of treatments. f Western blot analysis of cleaved PARP shows that the combination treatment significantly increases cleaved PARP activation. All data are shown as mean ± standard deviation ( n = 3). Statistically significant difference (Two-way ANOVA, Tukey’s post-hoc test) is shown as * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001 or ns (not significant).

Article Snippet: Val-083 (HY-16513) for in vitro testing and AZD1775 (HY-10993) were purchased from MedChemExpress, NJ, USA.

Techniques: Cell Cycle Assay, Modification, Apoptosis Assay, Western Blot, Activation Assay, Standard Deviation

a 24 h and 48 h scratch assay image captured using Olympus EP50 microscope. Scale bar = 300 µm. b Plot shows that percentage of wound recovery in the combination group is significantly reduced in comparison to vehicle and Val-083 groups after 24 and 48 h of treatment. c Transwell inserts captured using EVOS M5000 after 24 h and 48 h invasion assay. Scale bar = 150 µm. d Combination treatment significantly inhibits invasion of cells when compared to vehicle, Val-083 and AZD1775 treated groups after 48 h of treatment. e Western blot analysis of MMP2 and VEGF shows that AZD1775 and combination treatment significantly reduces expression of these proteins. All plots are shown as mean ± standard deviation ( n = 3). Statistically significant difference (One-way ANOVA or two-way ANOVA, Tukey’s post-hoc test) is shown as * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001 or ns (not significant).

Journal: NPJ Precision Oncology

Article Title: Dual treatment with Val-083 and AZD1775 shows potent anti-tumor activity in diffuse midline glioma models

doi: 10.1038/s41698-025-01006-4

Figure Lengend Snippet: a 24 h and 48 h scratch assay image captured using Olympus EP50 microscope. Scale bar = 300 µm. b Plot shows that percentage of wound recovery in the combination group is significantly reduced in comparison to vehicle and Val-083 groups after 24 and 48 h of treatment. c Transwell inserts captured using EVOS M5000 after 24 h and 48 h invasion assay. Scale bar = 150 µm. d Combination treatment significantly inhibits invasion of cells when compared to vehicle, Val-083 and AZD1775 treated groups after 48 h of treatment. e Western blot analysis of MMP2 and VEGF shows that AZD1775 and combination treatment significantly reduces expression of these proteins. All plots are shown as mean ± standard deviation ( n = 3). Statistically significant difference (One-way ANOVA or two-way ANOVA, Tukey’s post-hoc test) is shown as * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001 or ns (not significant).

Article Snippet: Val-083 (HY-16513) for in vitro testing and AZD1775 (HY-10993) were purchased from MedChemExpress, NJ, USA.

Techniques: Wound Healing Assay, Microscopy, Comparison, Invasion Assay, Western Blot, Expressing, Standard Deviation

a Schematic figure of treatment plans for SF8628 zebrafish xenograft models. b SF8628 zebrafish xenograft (midbrain) models at 4 days post injection (DPI) treated with vehicle, Val-083, AZD1775 and combination (combo) treatments. Scale bar = 750 µm. c SF8628 pericardial cavity tumor models of zebrafish at 4 DPI, treated with vehicle, Val-083, AZD1775 and combo treatments. Scale bar = 750 µm. d Migration of SF8628 cells to the tail region of zebrafish models. Scale bar = 750 µm. e Val-083 and AZD1775 as a single drug or as a combination shows significantly reduced tumor growth in the midbrain region, f pericardial cavity and ( g ) reduced migration of tumor cells towards the tail region after 3 days of treatment. All plots are shown as mean ± standard deviation ( n = 10 for midbrain; n = 10 for pericardial cavity). Statistically significant difference (One-way ANOVA, Tukey’s post-hoc test) is shown as ** p < 0.01; **** p < 0.0001.

Journal: NPJ Precision Oncology

Article Title: Dual treatment with Val-083 and AZD1775 shows potent anti-tumor activity in diffuse midline glioma models

doi: 10.1038/s41698-025-01006-4

Figure Lengend Snippet: a Schematic figure of treatment plans for SF8628 zebrafish xenograft models. b SF8628 zebrafish xenograft (midbrain) models at 4 days post injection (DPI) treated with vehicle, Val-083, AZD1775 and combination (combo) treatments. Scale bar = 750 µm. c SF8628 pericardial cavity tumor models of zebrafish at 4 DPI, treated with vehicle, Val-083, AZD1775 and combo treatments. Scale bar = 750 µm. d Migration of SF8628 cells to the tail region of zebrafish models. Scale bar = 750 µm. e Val-083 and AZD1775 as a single drug or as a combination shows significantly reduced tumor growth in the midbrain region, f pericardial cavity and ( g ) reduced migration of tumor cells towards the tail region after 3 days of treatment. All plots are shown as mean ± standard deviation ( n = 10 for midbrain; n = 10 for pericardial cavity). Statistically significant difference (One-way ANOVA, Tukey’s post-hoc test) is shown as ** p < 0.01; **** p < 0.0001.

Article Snippet: Val-083 (HY-16513) for in vitro testing and AZD1775 (HY-10993) were purchased from MedChemExpress, NJ, USA.

Techniques: Injection, Migration, Standard Deviation

a Schematic figure of SF8628 mice xenograft model treatment plans. b Survival curve of SF8628 mouse orthotopic tumor models treated with vehicle control, AZD1775, Val-083 and combination of both drugs. c Table indicates median survival of animals in different treatment groups. The combination treatment significantly extended survival of the animals in comparison to vehicle control and single treatments. d Images of H&E and IHC staining of tumor regions from harvested mouse brain of different treatment groups, captured using Olympus VS200. Scale bar = 100 µm. e IHC staining of cleaved caspase 3 shows that the combination treatment leads to significantly increased number of cells undergoing apoptosis in the Val-083, AZD1775 and combination groups. IHC staining of ( f ) Ki67 and ( g ) VEGF) shows no significant difference between treatment groups. All plots are shown as mean ± standard deviation ( n = 10 for survival curve; n = 3 for IHC). Statistically significant difference (One-way ANOVA, Tukey’s post-hoc test) is shown as * p < 0.05; ** p < 0.01; *** p < 0.001; and **** p < 0.0001.

Journal: NPJ Precision Oncology

Article Title: Dual treatment with Val-083 and AZD1775 shows potent anti-tumor activity in diffuse midline glioma models

doi: 10.1038/s41698-025-01006-4

Figure Lengend Snippet: a Schematic figure of SF8628 mice xenograft model treatment plans. b Survival curve of SF8628 mouse orthotopic tumor models treated with vehicle control, AZD1775, Val-083 and combination of both drugs. c Table indicates median survival of animals in different treatment groups. The combination treatment significantly extended survival of the animals in comparison to vehicle control and single treatments. d Images of H&E and IHC staining of tumor regions from harvested mouse brain of different treatment groups, captured using Olympus VS200. Scale bar = 100 µm. e IHC staining of cleaved caspase 3 shows that the combination treatment leads to significantly increased number of cells undergoing apoptosis in the Val-083, AZD1775 and combination groups. IHC staining of ( f ) Ki67 and ( g ) VEGF) shows no significant difference between treatment groups. All plots are shown as mean ± standard deviation ( n = 10 for survival curve; n = 3 for IHC). Statistically significant difference (One-way ANOVA, Tukey’s post-hoc test) is shown as * p < 0.05; ** p < 0.01; *** p < 0.001; and **** p < 0.0001.

Article Snippet: Val-083 (HY-16513) for in vitro testing and AZD1775 (HY-10993) were purchased from MedChemExpress, NJ, USA.

Techniques: Control, Comparison, Immunohistochemistry, Standard Deviation

Journal: Molecular cancer therapeutics

Article Title: Dianhydrogalactitol Overcomes Multiple Temozolomide Resistance Mechanisms in Glioblastoma

doi: 10.1158/1535-7163.MCT-20-0319

Figure Lengend Snippet: Val-083 cytotoxicity is exerted independently of MMR or MGMT expression. A, Viability of parental U-251 MG, T98G, U-87 MG, LN-18, and SF268 cell lines upon exposure to different concentrations of Val-083 measured by MTT. Values are represented as percentage of cell viability compared with DMSO control. B, Cell-cycle profile of U-251 MG or T98G cells treated with different doses of TMZ or Val-083 for 48 hours. C, Competition assay of U-251 MG cells expressing shRNAs targeting MSH6 (shMSH6.3908), PMS2 (shPMS2.946), and MSH2 (shMSH2.357) after treatment with TMZ or VAL-083. The plotted value is the fold enrichment of the shRNA-expressing cells (eGFP+) compared with the control cells (mCherry+) and normalized to the DMSO control. Statistical test: Two-way ANOVA (P values: *P < 0.05, **P < 0.01, compared with DMSO treated). D, CFA of U-251 MG cells expressing control shRNA or shMSH6 after treatment with TMZ or Val-083 for 9 days. E, Cell-cycle profile of U-251 MG cells expressing control shRNA (shRen.660) or shMSH6.3908 after treatment with TMZ or Val-083 for 48 hours. F, Quantification of mean γH2AX fluorescence in nuclei of cells treated with vehicle, TMZ, or Val-083 for 48 hours. Values are normalized to the DMSO control, and fold increase in H2AX signal is plotted. Statistical test: Two-way ANOVA (P values: ***, P < 0.001; ****, P < 0.0001, compared with DMSO treated).

Article Snippet: Different concentrations of TMZ (Merck, Catalog No. T2577), Val-083 (Adooq Bioscience, Catalog No. A15269), or DMSO (Sigma-Aldrich) were added.

Techniques: Expressing, Competitive Binding Assay, shRNA, Fluorescence

Journal: Molecular cancer therapeutics

Article Title: Dianhydrogalactitol Overcomes Multiple Temozolomide Resistance Mechanisms in Glioblastoma

doi: 10.1158/1535-7163.MCT-20-0319

Figure Lengend Snippet: TMZ and Val-083 combination treatment show synergistic cytotoxic effect. A, Table showing the percentage of cell viability (as compared with DMSO, top number in each cell) and SD (bottom number). B, Plot of synergy score calculated with the HSA method of U-251 MG cells treated with different doses of TMZ and Val-083. C, Table showing the maximum synergy scores of different adherent cell lines (U-251 MG, T98G, U-87 MG, SF268, LN-18) and tumorspheres grown in suspension (H543, H516, H676), as well as the doses of TMZ and Val-083, which rendered said score. MGMT expression is also indicated. D, CFA of U-251 MG cells incubated with low doses of TMZ, Val-083, or the combination for 9 days. E, Cell-cycle profile of U-251 MG cells incubated for 48 hours with TMZ, Val-083, or the combination of both. F, Representative pictures of γH2AX staining of U-251 MG cells treated for 48 hours with DMSO, TMZ, Val-083, or the combination of the last two. G, Quantification of γH2AX signal intensity in nuclei of U-251 MG cells treated for 48 hours with TMZ, Val-083, or the combination of both. Statistical test (P values: ***, P < 0.001). H, CFA of T98G cells incubated with high and low doses of TMZ, Val-083, or the combination for 9 days. I, Quantification of γH2AX signal intensity in nuclei of T98G cells treated for 48 hours with TMZ, Val-083, or the combination of both. Statistical test: t test (P values: *, P < 0.05; ***, P < 0.001).

Article Snippet: Different concentrations of TMZ (Merck, Catalog No. T2577), Val-083 (Adooq Bioscience, Catalog No. A15269), or DMSO (Sigma-Aldrich) were added.

Techniques: Expressing, Incubation, Staining

Journal: Molecular cancer therapeutics

Article Title: Dianhydrogalactitol Overcomes Multiple Temozolomide Resistance Mechanisms in Glioblastoma

doi: 10.1158/1535-7163.MCT-20-0319

Figure Lengend Snippet: Treatment with combination of TMZ and Val-083 increases survival in mice. A, Quantification of the ratio of luminescence emission by U251-MG in ex vivo-treated brain slices after 7 days as compared with the initial. Plots represent the fold change compared with the DMSO control. Statistical test: t test (P values: *, P < 0.05; **, P < 0.01; ***, P < 0.001; ns, nonsignficant); P values on top of the boxes are comparison over the DMSO control. B, Kaplan–Meier curve showing the survival proportions of mice transplanted with U-251 MG cells and treated with TMZ, Val-083, or the combination of both. Log-rank P values: **, P < 0.01; ns, nonsignificant). C, Kaplan–Meier curve showing the survival proportions of mice transplanted with H676 cells and treated with TMZ, Val-083, or the combination of both. Log-rank P values: **, P < 0.01; ns, nonsignificant).

Article Snippet: Different concentrations of TMZ (Merck, Catalog No. T2577), Val-083 (Adooq Bioscience, Catalog No. A15269), or DMSO (Sigma-Aldrich) were added.

Techniques: Ex Vivo

Journal: Molecular cancer therapeutics

Article Title: Dianhydrogalactitol Overcomes Multiple Temozolomide Resistance Mechanisms in Glioblastoma

doi: 10.1158/1535-7163.MCT-20-0319

Figure Lengend Snippet: Mechanisms of action of TMZ and Val-083. Expression of MGMT effectively removes the O6-guanine methylation induced by TMZ exposure, which allows cell survival. Lack of MGMT allows the formation of mismatches in the next replication round, which leads to the generation of double DNA-strand breaks mediated by the MMR machinery. The accumulation of double-strand breaks ultimately lead to cell death. However, defects in the MMR pathway paves the way for the accumulation of unresolved mismatches, which allows cell survival and a hypermutation phenotype. In the case of Val-083, there is a formation of interstrand adducts, that are not resolved by MGMT, and lead to cytotoxicity independently of MMR status.

Article Snippet: Different concentrations of TMZ (Merck, Catalog No. T2577), Val-083 (Adooq Bioscience, Catalog No. A15269), or DMSO (Sigma-Aldrich) were added.

Techniques: Expressing, Methylation

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