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vtp50469 (MedChemExpress)

Name: vtp50469
Brand: MedChemExpress
Rating: 93 (12 reviews)

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MedChemExpress vtp50469

( A ) Incucyte proliferation assay plotting percent confluence for A673 and TC32 cells treated with 0.1% DMSO or 10 µM <t>VTP50469</t> starting at time 0. Representative of n=3-4). ( B and C ) Invasion of cells from a sphere of A673 cells embedded in rat tail collagen and treated with 0.1% DMSO or 10 µM VTP50469 for 5 days. ( B ) Representative phase and phalloidin (red)/DAPI (blue) stained images are shown (scale bars=100 µm). ( C ) Plot of circularity quantified from replicate spheroids treated as in ( B ). ( D ) A673 and TC32 cells were treated with 0.1% DMSO or 10 µM VTP50469 for 72 hours and genes that were significantly downregulated in VTP50469-treated cells (padj<0.05) were overlapped with genes downregulated in MEN1-KO cells. The top 5 enriched Hallmark pathways for the overlapping downregulated genes in each cell line are shown along with the overlap/total genes for each pathway. The green arrows indicate pathways that were reactivated in A673 MEN1-KO tumors (see ). ( E ) MYC transcript levels in A673, CHLA10 and TC32 cells treated with 0.1% DMSO or 10 µM VTP50469 for 72 hours as determined by RT-qPCR (ns p > 0.05). ( F ) Western of MYC and Vinculin in cells treated with 0.1% DMSO or 10 µM VTP50469 for 72 hours. ( G ) Co-immunoprecipitations with an anti-Menin antibody were performed on nuclear extracts from A673 and CHLA10 cells treated with 0.1% DMSO or 10 µM VTP50469 for 72 hours and immunoblotted for Menin, MYC, MLL2 and WDR5.

Vtp50469, supplied by MedChemExpress, used in various techniques. Bioz Stars score: 93/100, based on 12 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
https://www.bioz.com/result/vtp50469/product/MedChemExpress
Average 93 stars, based on 12 article reviews

vtp50469 - by Bioz Stars, 2026-03

93/100 stars

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1) Product Images from "Menin inhibition impairs metastatic colonization of Ewing sarcoma"

Article Title: Menin inhibition impairs metastatic colonization of Ewing sarcoma

Journal: bioRxiv

doi: 10.1101/2025.11.10.687648

( A ) Incucyte proliferation assay plotting percent confluence for A673 and TC32 cells treated with 0.1% DMSO or 10 µM VTP50469 starting at time 0. Representative of n=3-4). ( B and C ) Invasion of cells from a sphere of A673 cells embedded in rat tail collagen and treated with 0.1% DMSO or 10 µM VTP50469 for 5 days. ( B ) Representative phase and phalloidin (red)/DAPI (blue) stained images are shown (scale bars=100 µm). ( C ) Plot of circularity quantified from replicate spheroids treated as in ( B ). ( D ) A673 and TC32 cells were treated with 0.1% DMSO or 10 µM VTP50469 for 72 hours and genes that were significantly downregulated in VTP50469-treated cells (padj<0.05) were overlapped with genes downregulated in MEN1-KO cells. The top 5 enriched Hallmark pathways for the overlapping downregulated genes in each cell line are shown along with the overlap/total genes for each pathway. The green arrows indicate pathways that were reactivated in A673 MEN1-KO tumors (see ). ( E ) MYC transcript levels in A673, CHLA10 and TC32 cells treated with 0.1% DMSO or 10 µM VTP50469 for 72 hours as determined by RT-qPCR (ns p > 0.05). ( F ) Western of MYC and Vinculin in cells treated with 0.1% DMSO or 10 µM VTP50469 for 72 hours. ( G ) Co-immunoprecipitations with an anti-Menin antibody were performed on nuclear extracts from A673 and CHLA10 cells treated with 0.1% DMSO or 10 µM VTP50469 for 72 hours and immunoblotted for Menin, MYC, MLL2 and WDR5.

Figure Legend Snippet: ( A ) Incucyte proliferation assay plotting percent confluence for A673 and TC32 cells treated with 0.1% DMSO or 10 µM VTP50469 starting at time 0. Representative of n=3-4). ( B and C ) Invasion of cells from a sphere of A673 cells embedded in rat tail collagen and treated with 0.1% DMSO or 10 µM VTP50469 for 5 days. ( B ) Representative phase and phalloidin (red)/DAPI (blue) stained images are shown (scale bars=100 µm). ( C ) Plot of circularity quantified from replicate spheroids treated as in ( B ). ( D ) A673 and TC32 cells were treated with 0.1% DMSO or 10 µM VTP50469 for 72 hours and genes that were significantly downregulated in VTP50469-treated cells (padj<0.05) were overlapped with genes downregulated in MEN1-KO cells. The top 5 enriched Hallmark pathways for the overlapping downregulated genes in each cell line are shown along with the overlap/total genes for each pathway. The green arrows indicate pathways that were reactivated in A673 MEN1-KO tumors (see ). ( E ) MYC transcript levels in A673, CHLA10 and TC32 cells treated with 0.1% DMSO or 10 µM VTP50469 for 72 hours as determined by RT-qPCR (ns p > 0.05). ( F ) Western of MYC and Vinculin in cells treated with 0.1% DMSO or 10 µM VTP50469 for 72 hours. ( G ) Co-immunoprecipitations with an anti-Menin antibody were performed on nuclear extracts from A673 and CHLA10 cells treated with 0.1% DMSO or 10 µM VTP50469 for 72 hours and immunoblotted for Menin, MYC, MLL2 and WDR5.

Techniques Used: Proliferation Assay, Staining, Quantitative RT-PCR, Western Blot

( A ) Diagram of mouse experiment. 5e4 A673 GFP-Luciferase cells were injected into the tail veins of 30 NSG mice (male and female) and 7 days later mice randomized to regular (control) or 0.1% VTP50469 mouse chow (∼120-180 mg/kg/day). Four VTP50469-treated mice were taken off drug at study end and followed for up to 41 days as described in text. ( B ) Spider plots of IVIS signal for each control and VTP50469-treated mouse. ( C) Plot of time to engraftment with engraftment set at an IVIS signal of 1e8. ( D ) Luminescence of all mice at 33 days post-injection. Sex of each mouse is indicated (M=male, F=female). ( E ) Survival plot comparing the control and VTP50469-treated mice. ( F ) Images of representative livers from the control and VTP50469-treated mice are shown (scale bar=1 cm). The number of macroscopic tumors in the livers was counted and plotted for each mouse. ( G ) Spider plot of IVIS signals from 4 mice taken off VTP50469 and followed. The liver of one of the released mice (* in G ) is shown.

Figure Legend Snippet: ( A ) Diagram of mouse experiment. 5e4 A673 GFP-Luciferase cells were injected into the tail veins of 30 NSG mice (male and female) and 7 days later mice randomized to regular (control) or 0.1% VTP50469 mouse chow (∼120-180 mg/kg/day). Four VTP50469-treated mice were taken off drug at study end and followed for up to 41 days as described in text. ( B ) Spider plots of IVIS signal for each control and VTP50469-treated mouse. ( C) Plot of time to engraftment with engraftment set at an IVIS signal of 1e8. ( D ) Luminescence of all mice at 33 days post-injection. Sex of each mouse is indicated (M=male, F=female). ( E ) Survival plot comparing the control and VTP50469-treated mice. ( F ) Images of representative livers from the control and VTP50469-treated mice are shown (scale bar=1 cm). The number of macroscopic tumors in the livers was counted and plotted for each mouse. ( G ) Spider plot of IVIS signals from 4 mice taken off VTP50469 and followed. The liver of one of the released mice (* in G ) is shown.

Techniques Used: Luciferase, Injection, Control

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Journal: bioRxiv

Article Title: Menin inhibition impairs metastatic colonization of Ewing sarcoma

doi: 10.1101/2025.11.10.687648

Figure Lengend Snippet: ( A ) Incucyte proliferation assay plotting percent confluence for A673 and TC32 cells treated with 0.1% DMSO or 10 µM VTP50469 starting at time 0. Representative of n=3-4). ( B and C ) Invasion of cells from a sphere of A673 cells embedded in rat tail collagen and treated with 0.1% DMSO or 10 µM VTP50469 for 5 days. ( B ) Representative phase and phalloidin (red)/DAPI (blue) stained images are shown (scale bars=100 µm). ( C ) Plot of circularity quantified from replicate spheroids treated as in ( B ). ( D ) A673 and TC32 cells were treated with 0.1% DMSO or 10 µM VTP50469 for 72 hours and genes that were significantly downregulated in VTP50469-treated cells (padj<0.05) were overlapped with genes downregulated in MEN1-KO cells. The top 5 enriched Hallmark pathways for the overlapping downregulated genes in each cell line are shown along with the overlap/total genes for each pathway. The green arrows indicate pathways that were reactivated in A673 MEN1-KO tumors (see ). ( E ) MYC transcript levels in A673, CHLA10 and TC32 cells treated with 0.1% DMSO or 10 µM VTP50469 for 72 hours as determined by RT-qPCR (ns p > 0.05). ( F ) Western of MYC and Vinculin in cells treated with 0.1% DMSO or 10 µM VTP50469 for 72 hours. ( G ) Co-immunoprecipitations with an anti-Menin antibody were performed on nuclear extracts from A673 and CHLA10 cells treated with 0.1% DMSO or 10 µM VTP50469 for 72 hours and immunoblotted for Menin, MYC, MLL2 and WDR5.

Article Snippet: To inhibit Menin, cells were treated with 0.1% DMSO (Vehicle) or 10 μM VTP50469 (MedChemExpress HY-114162) for 72 hours.

Techniques: Proliferation Assay, Staining, Quantitative RT-PCR, Western Blot

Journal: bioRxiv

Article Title: Menin inhibition impairs metastatic colonization of Ewing sarcoma

doi: 10.1101/2025.11.10.687648

Figure Lengend Snippet: ( A ) Diagram of mouse experiment. 5e4 A673 GFP-Luciferase cells were injected into the tail veins of 30 NSG mice (male and female) and 7 days later mice randomized to regular (control) or 0.1% VTP50469 mouse chow (∼120-180 mg/kg/day). Four VTP50469-treated mice were taken off drug at study end and followed for up to 41 days as described in text. ( B ) Spider plots of IVIS signal for each control and VTP50469-treated mouse. ( C) Plot of time to engraftment with engraftment set at an IVIS signal of 1e8. ( D ) Luminescence of all mice at 33 days post-injection. Sex of each mouse is indicated (M=male, F=female). ( E ) Survival plot comparing the control and VTP50469-treated mice. ( F ) Images of representative livers from the control and VTP50469-treated mice are shown (scale bar=1 cm). The number of macroscopic tumors in the livers was counted and plotted for each mouse. ( G ) Spider plot of IVIS signals from 4 mice taken off VTP50469 and followed. The liver of one of the released mice (* in G ) is shown.

Article Snippet: To inhibit Menin, cells were treated with 0.1% DMSO (Vehicle) or 10 μM VTP50469 (MedChemExpress HY-114162) for 72 hours.

Techniques: Luciferase, Injection, Control

(A) Stacked bar plots showing distributions of CUT&RUN data from DMSO-treated NPM1 WT/Degron OCI-AML3 cells, with genomic peaks annotated as TSSs, promoters, exons, introns, and intergenic regions. (B) Venn diagram of TSS-promoter peaks from DMSO-treated CUT&RUN sequencing depicting unique genes bound by at least 3 of 4 antibody targets (including XPO1, NUP98, KMT2A, and MENIN) ( n = 235) and NPM1c target genes identified by ChIP-seq ( n = 33, Uckelmann et al. 2023) and annotated table of genes found in both datasets. (C) RDF of NUP98 and HOXA9 in top (red) and bottom (purple) quartiles in comparison to the average ( n = 69). (D) Immunoblotting analysis of protein lysates from OCI-AML3 and IMS-m2 cells treated with DMSO or dTAG for 72h using anti-GFP, anti-NPM1wt and anti-Gapdh-Rhodamine antibodies. (E) Relative mRNA levels of HOXA/MEIS1 in OCI-AML3 cells treated with VTP50469 or Selinexor. (F) Mean CD11b level in OCI-AML3 cells treated with VTP50469, dTAG-13, Selinexor or DMSO for 4 weeks and (G) representative histograms of CD11b level. (H) Representative Integrated Genome Viewer (IGV) tracks (duplicates per sample) for IgG (black), H3K27me3 (Gray), XPO1 (Red), NUP98 (Blue), KMT2A (Green), and MENIN (Orange) treated with DMSO, dTAG-13 (500nM), Eltanexor (100nM), or VTP50469 (300nM) for 24 hours. Fisher’s Exact test was used for statistical testing.

Journal: bioRxiv

Article Title: Nuclear Phase Separation Drives NPM1-mutant Acute Myeloid Leukemia

doi: 10.1101/2025.05.23.655671

Figure Lengend Snippet: (A) Stacked bar plots showing distributions of CUT&RUN data from DMSO-treated NPM1 WT/Degron OCI-AML3 cells, with genomic peaks annotated as TSSs, promoters, exons, introns, and intergenic regions. (B) Venn diagram of TSS-promoter peaks from DMSO-treated CUT&RUN sequencing depicting unique genes bound by at least 3 of 4 antibody targets (including XPO1, NUP98, KMT2A, and MENIN) ( n = 235) and NPM1c target genes identified by ChIP-seq ( n = 33, Uckelmann et al. 2023) and annotated table of genes found in both datasets. (C) RDF of NUP98 and HOXA9 in top (red) and bottom (purple) quartiles in comparison to the average ( n = 69). (D) Immunoblotting analysis of protein lysates from OCI-AML3 and IMS-m2 cells treated with DMSO or dTAG for 72h using anti-GFP, anti-NPM1wt and anti-Gapdh-Rhodamine antibodies. (E) Relative mRNA levels of HOXA/MEIS1 in OCI-AML3 cells treated with VTP50469 or Selinexor. (F) Mean CD11b level in OCI-AML3 cells treated with VTP50469, dTAG-13, Selinexor or DMSO for 4 weeks and (G) representative histograms of CD11b level. (H) Representative Integrated Genome Viewer (IGV) tracks (duplicates per sample) for IgG (black), H3K27me3 (Gray), XPO1 (Red), NUP98 (Blue), KMT2A (Green), and MENIN (Orange) treated with DMSO, dTAG-13 (500nM), Eltanexor (100nM), or VTP50469 (300nM) for 24 hours. Fisher’s Exact test was used for statistical testing.

Article Snippet: To inhibit the KMT2A-MENIN interaction, cells were treated with 300nM VTP50469 (Selleckchem, S8934) or 2.5μM MI-503 (Selleckchem, S7817).

Techniques: Sequencing, ChIP-sequencing, Comparison, Western Blot

(A) Live cell imaging of NPM1 WT/Degron OCI-AML3 cells treated with DMSO, dTAG-13, Eltanexor, or VTP50469. (B) Quantification of NPM1c concentration across compartments after drug treatments ( n = 50). (C-F) Immunostaining of NPM1 WT/Degron OCI-AML3 cells with antibodies targeting XPO1, NUP98, KMT2A, and MENIN after specific drug treatments. (G) Quantification of max protein enrichment in the nucleoplasm ( n = 50). (H) Enrichment of NPM1c protein within max enriched ROI ( n = 50). (I) RDF of XPO1, NUP98, KMT2A, and MENIN with DMSO or VTP50469 treatment, ( n = 50). All cells were treated at same concentrations for 24hrs prior to live cell imaging or immunostaining (dTAG-13 = 500nM, Eltanexor = 100nM, VTP50469 = 300nM). All images are shown in Fire LUT except colocalization (cyan and magenta). White scale bars = 2µm. All insets are magnified 2µm square regions. For image analysis, the brightest region containing NPM1c or other protein in the nucleus is identified (0.15µm 2 box) in individual cells and concentration (photons at reference settings) is measured and normalized to untreated controls.

Journal: bioRxiv

Article Title: Nuclear Phase Separation Drives NPM1-mutant Acute Myeloid Leukemia

doi: 10.1101/2025.05.23.655671

Figure Lengend Snippet: (A) Live cell imaging of NPM1 WT/Degron OCI-AML3 cells treated with DMSO, dTAG-13, Eltanexor, or VTP50469. (B) Quantification of NPM1c concentration across compartments after drug treatments ( n = 50). (C-F) Immunostaining of NPM1 WT/Degron OCI-AML3 cells with antibodies targeting XPO1, NUP98, KMT2A, and MENIN after specific drug treatments. (G) Quantification of max protein enrichment in the nucleoplasm ( n = 50). (H) Enrichment of NPM1c protein within max enriched ROI ( n = 50). (I) RDF of XPO1, NUP98, KMT2A, and MENIN with DMSO or VTP50469 treatment, ( n = 50). All cells were treated at same concentrations for 24hrs prior to live cell imaging or immunostaining (dTAG-13 = 500nM, Eltanexor = 100nM, VTP50469 = 300nM). All images are shown in Fire LUT except colocalization (cyan and magenta). White scale bars = 2µm. All insets are magnified 2µm square regions. For image analysis, the brightest region containing NPM1c or other protein in the nucleus is identified (0.15µm 2 box) in individual cells and concentration (photons at reference settings) is measured and normalized to untreated controls.

Article Snippet: To inhibit the KMT2A-MENIN interaction, cells were treated with 300nM VTP50469 (Selleckchem, S8934) or 2.5μM MI-503 (Selleckchem, S7817).

Techniques: Live Cell Imaging, Concentration Assay, Immunostaining, Protein Enrichment

(A) Npm1c induction with tamoxifen in mice (LEFT) and immunostaining of HSPCs isolated from NPM1frtC and NPM1c donor mice with anti-NUP98 (cyan) and anti-MENIN (magenta) antibodies. (B) Schematic representation of Npm1c AML model development for ex vivo studies. (C) Immunostaining of murine HSPCs treated with DMSO or VTP50469 ex vivo with anti-NUP98 (cyan) and anti-MENIN (magenta) antibodies. (D) Real-time qPCR analysis of Hoxa9 , Hoxa10 and Meis1 mRNA levels and (E) flow cytometry analysis of myeloid differentiation markers Gr1 and Mac1 (MFI) in murine HSPCs treated with DMSO or VTP50469 ex vivo . (F) Immunostaining of human AML patient cells treated with DMSO or VTP50469 ex vivo with anti-NUP98 (cyan) and anti-MENIN (magenta) antibodies. (G) RDF of NUP98 and MENIN with DMSO or VTP50469 treatment ( n = 20-60 cells per sample). (H) Representative histogram of CD11b fluorescence intensity in DMSO and VTP50469. (I) Fold change of mean CD11b fluorescence level in patient samples relative to DMSO cells. All cells were treated at the same concentrations for 24hrs prior to live cell imaging or immunostaining. Flow cytometry analysis was performed at day 3 and day 6 in human and murine cells respectively.

Journal: bioRxiv

Article Title: Nuclear Phase Separation Drives NPM1-mutant Acute Myeloid Leukemia

doi: 10.1101/2025.05.23.655671

Figure Lengend Snippet: (A) Npm1c induction with tamoxifen in mice (LEFT) and immunostaining of HSPCs isolated from NPM1frtC and NPM1c donor mice with anti-NUP98 (cyan) and anti-MENIN (magenta) antibodies. (B) Schematic representation of Npm1c AML model development for ex vivo studies. (C) Immunostaining of murine HSPCs treated with DMSO or VTP50469 ex vivo with anti-NUP98 (cyan) and anti-MENIN (magenta) antibodies. (D) Real-time qPCR analysis of Hoxa9 , Hoxa10 and Meis1 mRNA levels and (E) flow cytometry analysis of myeloid differentiation markers Gr1 and Mac1 (MFI) in murine HSPCs treated with DMSO or VTP50469 ex vivo . (F) Immunostaining of human AML patient cells treated with DMSO or VTP50469 ex vivo with anti-NUP98 (cyan) and anti-MENIN (magenta) antibodies. (G) RDF of NUP98 and MENIN with DMSO or VTP50469 treatment ( n = 20-60 cells per sample). (H) Representative histogram of CD11b fluorescence intensity in DMSO and VTP50469. (I) Fold change of mean CD11b fluorescence level in patient samples relative to DMSO cells. All cells were treated at the same concentrations for 24hrs prior to live cell imaging or immunostaining. Flow cytometry analysis was performed at day 3 and day 6 in human and murine cells respectively.

Article Snippet: To inhibit the KMT2A-MENIN interaction, cells were treated with 300nM VTP50469 (Selleckchem, S8934) or 2.5μM MI-503 (Selleckchem, S7817).

Techniques: Immunostaining, Isolation, Ex Vivo, Flow Cytometry, Fluorescence, Live Cell Imaging

$Negative selection competition assays in OCI-AML2 cells resistant and sensitive to Menin inhibition expressing Cas9 and guide RNAs targeting KAT6A or BRPF1 ( a ) and KAT7 or ING5 ( b ). Values represent fraction of RFP-positive CRISPR/Cas9 knockout cells relative to baseline. c , Percentage of human CD45-positive cells in peripheral blood of mice transplanted with PDX049D and treated with 0.03% VTP50469 (in rodent diet). d , Percentage of human CD45-positive cells in the bone marrow and peripheral blood of NOG mice transplanted with Menin resistant PDX049D treated with vehicle, 0.1% VTP50469 (in rodent diet) or 5 mg/kg PF-9363 (intraperitoneal injection) for 14 days. e , Molm-13 cells were treated for 96 hr with indicated doses of PF-9363 and/or VTP50469. Values indicate the percentage of non-viable cells relative to indicated doses of drug. The mean and median of the percent non-viable cells across all conditions are displayed above the heatmap. f , Summary table of Bliss synergy scores between PF-9363 and VTP50469 for indicated leukaemia cell lines, Molm-13, MV4;11, THP-1 and MLL-AF9. Synergy scores were calculated using the Bliss method. Max synergy scores are defined as the Bliss synergy score that corresponds to the combination of the highest concentration of both drugs, 1 µM VTP50469 and 2.5 µM PF-9363.$

Journal: bioRxiv

Article Title: Catalytic inhibition of KAT6/KAT7 enhances the efficacy and overcomes primary and acquired resistance to Menin inhibitors in MLL leukaemia

doi: 10.1101/2024.12.11.627663

Figure Lengend Snippet: Negative selection competition assays in OCI-AML2 cells resistant and sensitive to Menin inhibition expressing Cas9 and guide RNAs targeting KAT6A or BRPF1 ( a ) and KAT7 or ING5 ( b ). Values represent fraction of RFP-positive CRISPR/Cas9 knockout cells relative to baseline. c , Percentage of human CD45-positive cells in peripheral blood of mice transplanted with PDX049D and treated with 0.03% VTP50469 (in rodent diet). d , Percentage of human CD45-positive cells in the bone marrow and peripheral blood of NOG mice transplanted with Menin resistant PDX049D treated with vehicle, 0.1% VTP50469 (in rodent diet) or 5 mg/kg PF-9363 (intraperitoneal injection) for 14 days. e , Molm-13 cells were treated for 96 hr with indicated doses of PF-9363 and/or VTP50469. Values indicate the percentage of non-viable cells relative to indicated doses of drug. The mean and median of the percent non-viable cells across all conditions are displayed above the heatmap. f , Summary table of Bliss synergy scores between PF-9363 and VTP50469 for indicated leukaemia cell lines, Molm-13, MV4;11, THP-1 and MLL-AF9. Synergy scores were calculated using the Bliss method. Max synergy scores are defined as the Bliss synergy score that corresponds to the combination of the highest concentration of both drugs, 1 µM VTP50469 and 2.5 µM PF-9363.

Article Snippet: PF-9363 and VTP50469 were dispensed using the D300e Digital Dispenser (Tecan) and incubated for 96 hours.

Techniques: Selection, Inhibition, Expressing, CRISPR, Knock-Out, Injection, Concentration Assay

Combination of PF-9363 and VTP50469 induces rapid shutdown of the leukemic transcriptional program Volcano plot showing differential gene expression of Molm-13 cells treated for 6 hr with 2.5 µM PF-9363 versus vehicle ( a ), 100 nM VTP50469 versus vehicle ( b ) or combination (2.5 µM PF- 9363 and 100 nM VTP50469) versus vehicle ( c ). Significant differentially expressed genes are defined as genes with an adjusted p-value < 0.05 and absolute log2 fold change of 1. d , Heatmap showing the top 50 differentially expressed genes by adjusted p-value for the combination versus vehicle treatment groups after 6 hr of treatment. Key targets of the MLL-AF9 oncogene, MEIS1 PBX3, HOXA9, REEP3 and JMJD1C are highlighted in red. Row scaled Z- scores are shown. PF = 2.5 µM PF-9363 treatment group, VTP = 100 nM VTP50469 treatment group. GSEA of the BROWN_MYELOID_CELL_DEVELOPMENT gene set (e) and the GILAN_MLLAF9_Targets gene set ( f ) for the combination versus vehicle treatment groups. Positive scores indicate enrichment in the combination group. Negative scores indicate enrichment in the vehicle group. g , Chromatin immunoprecipitation for MLL1 and Menin in Molm-13 cells treated for 24 hr with vehicle or combination (2.5 µM PF-9363 and 100 nM VTP50469). Genome browser snapshots of PBX3 , HOXA cluster, MEIS1, REEP3 and JMJD1C .

Journal: bioRxiv

Article Title: Catalytic inhibition of KAT6/KAT7 enhances the efficacy and overcomes primary and acquired resistance to Menin inhibitors in MLL leukaemia

doi: 10.1101/2024.12.11.627663

Figure Lengend Snippet: Combination of PF-9363 and VTP50469 induces rapid shutdown of the leukemic transcriptional program Volcano plot showing differential gene expression of Molm-13 cells treated for 6 hr with 2.5 µM PF-9363 versus vehicle ( a ), 100 nM VTP50469 versus vehicle ( b ) or combination (2.5 µM PF- 9363 and 100 nM VTP50469) versus vehicle ( c ). Significant differentially expressed genes are defined as genes with an adjusted p-value < 0.05 and absolute log2 fold change of 1. d , Heatmap showing the top 50 differentially expressed genes by adjusted p-value for the combination versus vehicle treatment groups after 6 hr of treatment. Key targets of the MLL-AF9 oncogene, MEIS1 PBX3, HOXA9, REEP3 and JMJD1C are highlighted in red. Row scaled Z- scores are shown. PF = 2.5 µM PF-9363 treatment group, VTP = 100 nM VTP50469 treatment group. GSEA of the BROWN_MYELOID_CELL_DEVELOPMENT gene set (e) and the GILAN_MLLAF9_Targets gene set ( f ) for the combination versus vehicle treatment groups. Positive scores indicate enrichment in the combination group. Negative scores indicate enrichment in the vehicle group. g , Chromatin immunoprecipitation for MLL1 and Menin in Molm-13 cells treated for 24 hr with vehicle or combination (2.5 µM PF-9363 and 100 nM VTP50469). Genome browser snapshots of PBX3 , HOXA cluster, MEIS1, REEP3 and JMJD1C .

Article Snippet: PF-9363 and VTP50469 were dispensed using the D300e Digital Dispenser (Tecan) and incubated for 96 hours.

Techniques: Expressing, Chromatin Immunoprecipitation

Single cell RNA-Seq reveals clone dependent responses to combined PF-9363 and VTP50469 a, UMAP of scRNA-sequencing dataset composed of samples from T0 (light blue), vehicle (dark blue) and combination (red) groups from 24,906 cells. b , UMAP annotated with the normalised expression of HOXA9 and MEIS1 in T0, vehicle and combination groups. c , GSEA plots of Inflammatory Response, TNF-alpha signalling through NFKB, IL6_JAK_STAT3 signalling, and Interferon Gamma Responsive gene sets in the combination group versus the vehicle group. Positive scores indicate enrichment in the combination group. Negative scores indicate enrichment in the vehicle group. d , UMAP of vehicle and combination treatment groups (left) and UMAP annotated for cells comprising non-responsive clones (right). e , Heatmap of differentially expressed genes identified from pairwise comparisons of non- responsive clones in the combination treatment group. Heatmap shows row-scaled normalised expression values. f , UMAP annotated with the normalised expression of SLPI across T0, vehicle and combination groups. g , Violin plot of SLPI expression in vehicle versus combination treatment groups. Wilcox test. h , Violin plots of HOXA9 (left), MEIS1 (centre) and SLPI (right) expression in the vehicle treatment group for non-responsive clones 465713 and 522483. Other clones represent clones responsive to combination treatment. Wilcox test.

Journal: bioRxiv

Article Title: Catalytic inhibition of KAT6/KAT7 enhances the efficacy and overcomes primary and acquired resistance to Menin inhibitors in MLL leukaemia

doi: 10.1101/2024.12.11.627663

Figure Lengend Snippet: Single cell RNA-Seq reveals clone dependent responses to combined PF-9363 and VTP50469 a, UMAP of scRNA-sequencing dataset composed of samples from T0 (light blue), vehicle (dark blue) and combination (red) groups from 24,906 cells. b , UMAP annotated with the normalised expression of HOXA9 and MEIS1 in T0, vehicle and combination groups. c , GSEA plots of Inflammatory Response, TNF-alpha signalling through NFKB, IL6_JAK_STAT3 signalling, and Interferon Gamma Responsive gene sets in the combination group versus the vehicle group. Positive scores indicate enrichment in the combination group. Negative scores indicate enrichment in the vehicle group. d , UMAP of vehicle and combination treatment groups (left) and UMAP annotated for cells comprising non-responsive clones (right). e , Heatmap of differentially expressed genes identified from pairwise comparisons of non- responsive clones in the combination treatment group. Heatmap shows row-scaled normalised expression values. f , UMAP annotated with the normalised expression of SLPI across T0, vehicle and combination groups. g , Violin plot of SLPI expression in vehicle versus combination treatment groups. Wilcox test. h , Violin plots of HOXA9 (left), MEIS1 (centre) and SLPI (right) expression in the vehicle treatment group for non-responsive clones 465713 and 522483. Other clones represent clones responsive to combination treatment. Wilcox test.

Article Snippet: PF-9363 and VTP50469 were dispensed using the D300e Digital Dispenser (Tecan) and incubated for 96 hours.

Techniques: RNA Sequencing Assay, Sequencing, Expressing, Clone Assay

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