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View article: Supplemental Table 5 from KT-253, a Novel MDM2 Degrader and p53 Stabilizer, Has Superior Potency and Efficacy than MDM2 Small-Molecule Inhibitors
Supplemental Table 5 from KT-253, a Novel MDM2 Degrader and p53 Stabilizer, Has Superior Potency and Efficacy than MDM2 Small-Molecule Inhibitors Open
Supplemental Table 5: Activity of KT-253 in AML patient-derived xenograft models.
View article: Supplemental Table 2 from KT-253, a Novel MDM2 Degrader and p53 Stabilizer, Has Superior Potency and Efficacy than MDM2 Small-Molecule Inhibitors
Supplemental Table 2 from KT-253, a Novel MDM2 Degrader and p53 Stabilizer, Has Superior Potency and Efficacy than MDM2 Small-Molecule Inhibitors Open
Supplemental Table 2: Genes and TaqMan Gene Expression Assay IDs used for RT-qPCR assays
View article: Supplemental Table 4 from KT-253, a Novel MDM2 Degrader and p53 Stabilizer, Has Superior Potency and Efficacy than MDM2 Small-Molecule Inhibitors
Supplemental Table 4 from KT-253, a Novel MDM2 Degrader and p53 Stabilizer, Has Superior Potency and Efficacy than MDM2 Small-Molecule Inhibitors Open
Supplemental Table 4: KT-253 shows potent growth inhibition and caspase activation across a panel of p53 wild-type hematologic cell lines.
View article: Supplemental Table 1 from KT-253, a Novel MDM2 Degrader and p53 Stabilizer, Has Superior Potency and Efficacy than MDM2 Small-Molecule Inhibitors
Supplemental Table 1 from KT-253, a Novel MDM2 Degrader and p53 Stabilizer, Has Superior Potency and Efficacy than MDM2 Small-Molecule Inhibitors Open
Supplemental Table 1: Cell lines and reagents
View article: Supplemental Figure 7 from KT-253, a Novel MDM2 Degrader and p53 Stabilizer, Has Superior Potency and Efficacy than MDM2 Small-Molecule Inhibitors
Supplemental Figure 7 from KT-253, a Novel MDM2 Degrader and p53 Stabilizer, Has Superior Potency and Efficacy than MDM2 Small-Molecule Inhibitors Open
Supplemental Figure 7: A single dose of KT 253 shows strong single-agent activity in a venetoclax resistant patient-derived AML model.
View article: Data from KT-253, a Novel MDM2 Degrader and p53 Stabilizer, Has Superior Potency and Efficacy than MDM2 Small-Molecule Inhibitors
Data from KT-253, a Novel MDM2 Degrader and p53 Stabilizer, Has Superior Potency and Efficacy than MDM2 Small-Molecule Inhibitors Open
Murine double minute 2 (MDM2) is an E3 ligase that inhibits the tumor suppressor protein p53. Clinical trials employing small-molecule MDM2/p53 interaction inhibitors have demonstrated limited activity, underscoring an unmet need for a bet…
View article: Supplemental Figure 1 from KT-253, a Novel MDM2 Degrader and p53 Stabilizer, Has Superior Potency and Efficacy than MDM2 Small-Molecule Inhibitors
Supplemental Figure 1 from KT-253, a Novel MDM2 Degrader and p53 Stabilizer, Has Superior Potency and Efficacy than MDM2 Small-Molecule Inhibitors Open
Supplemental Figure 1: Chemical structures of (A) Compound 1, a KT 253 analog that lacks ability to engage cereblon (CRBN), (B) Compound 2, the warhead of KT 253 that engages MDM2, and (C) DS-3032, a small-molecule MDM2/p53 interaction inh…
View article: Supplemental Figure 3 from KT-253, a Novel MDM2 Degrader and p53 Stabilizer, Has Superior Potency and Efficacy than MDM2 Small-Molecule Inhibitors
Supplemental Figure 3 from KT-253, a Novel MDM2 Degrader and p53 Stabilizer, Has Superior Potency and Efficacy than MDM2 Small-Molecule Inhibitors Open
Supplemental Figure 3: Short term exposures with KT-253 sufficient for growth inhibition compared with MDM2 SMIs.
View article: Supplemental Figure 2 from KT-253, a Novel MDM2 Degrader and p53 Stabilizer, Has Superior Potency and Efficacy than MDM2 Small-Molecule Inhibitors
Supplemental Figure 2 from KT-253, a Novel MDM2 Degrader and p53 Stabilizer, Has Superior Potency and Efficacy than MDM2 Small-Molecule Inhibitors Open
Supplemental Figure 2: Targeted proteomics analysis of MDM2 levels in MV4;11 AML cells shows that 150 nM KT 253 can achieve degradation of MDM2 within 1 hour posttreatment.
View article: Supplemental Table 3 from KT-253, a Novel MDM2 Degrader and p53 Stabilizer, Has Superior Potency and Efficacy than MDM2 Small-Molecule Inhibitors
Supplemental Table 3 from KT-253, a Novel MDM2 Degrader and p53 Stabilizer, Has Superior Potency and Efficacy than MDM2 Small-Molecule Inhibitors Open
Supplemental Table 3: KT-253 shows picomolar growth inhibition potency compared with other MDM2 small molecule inhibitors.
View article: Supplemental Figure 4 from KT-253, a Novel MDM2 Degrader and p53 Stabilizer, Has Superior Potency and Efficacy than MDM2 Small-Molecule Inhibitors
Supplemental Figure 4 from KT-253, a Novel MDM2 Degrader and p53 Stabilizer, Has Superior Potency and Efficacy than MDM2 Small-Molecule Inhibitors Open
Supplemental Figure 4: A functional p53 is required for growth inhibition with KT-253.
View article: Supplemental Figure 6 from KT-253, a Novel MDM2 Degrader and p53 Stabilizer, Has Superior Potency and Efficacy than MDM2 Small-Molecule Inhibitors
Supplemental Figure 6 from KT-253, a Novel MDM2 Degrader and p53 Stabilizer, Has Superior Potency and Efficacy than MDM2 Small-Molecule Inhibitors Open
Supplemental Figure 6: KT 253 activity in p53 WT ABC subtype DLBCL model but not p53 mutated ABC subtype DLBCL model.
View article: Supplemental Figure 5 from KT-253, a Novel MDM2 Degrader and p53 Stabilizer, Has Superior Potency and Efficacy than MDM2 Small-Molecule Inhibitors
Supplemental Figure 5 from KT-253, a Novel MDM2 Degrader and p53 Stabilizer, Has Superior Potency and Efficacy than MDM2 Small-Molecule Inhibitors Open
Supplemental Figure 5: A single dose of KT-253 more robustly induces p53 targets compared with exposure matched weekly dosing regimen.
View article: Identification of small molecule inhibitors of PPM1D using an integrated drug discovery platform
Identification of small molecule inhibitors of PPM1D using an integrated drug discovery platform Open
PPM1D is a serine/threonine phosphatase recurrently activated in cancer, regulates the DNA damage response (DDR), and suppresses p53. Though PPM1D inhibition impairs tumor growth in cancer models and is the subject of multiple drug discove…
View article: KT-253, a Novel MDM2 Degrader and p53 Stabilizer, Has Superior Potency and Efficacy than MDM2 Small-Molecule Inhibitors
KT-253, a Novel MDM2 Degrader and p53 Stabilizer, Has Superior Potency and Efficacy than MDM2 Small-Molecule Inhibitors Open
Murine double minute 2 (MDM2) is an E3 ligase that inhibits the tumor suppressor protein p53. Clinical trials employing small-molecule MDM2/p53 interaction inhibitors have demonstrated limited activity, underscoring an unmet need for a bet…
View article: Identification of Small Molecule Inhibitors of PPM1D Using a Novel Drug Discovery Platform
Identification of Small Molecule Inhibitors of PPM1D Using a Novel Drug Discovery Platform Open
Protein phosphatase, Mg 2+ /Mn 2+ dependent 1D (PPM1D), is a serine/threonine phosphatase that is recurrently activated in cancer, regulates the DNA damage response (DDR), and suppresses the activation of p53. Consistent with its oncogenic…
View article: P464: PULSE DOSING OF POTENT AND SELECTIVE HETEROBIFUNCTIONAL MDM2 DEGRADER KT-253 DRIVES TUMOR REGRESSION AND DEMONSTRATES DIFFERENTIATED PHARMACOLOGY COMPARED TO P53/MDM2 SMALL MOLECULE INHIBITORS.
P464: PULSE DOSING OF POTENT AND SELECTIVE HETEROBIFUNCTIONAL MDM2 DEGRADER KT-253 DRIVES TUMOR REGRESSION AND DEMONSTRATES DIFFERENTIATED PHARMACOLOGY COMPARED TO P53/MDM2 SMALL MOLECULE INHIBITORS. Open
Background: The murine double minute 2 (MDM2) oncoprotein is a key E3 ubiquitin ligase that degrades the tumor-suppressor p53. Targeting of the MDM2/p53 interaction to stabilize p53 and induce apoptosis in wildtype (WT) p53 tumors is an em…
View article: Supplementary Figures and Tables from A Ubiquitination Cascade Regulating the Integrated Stress Response and Survival in Carcinomas
Supplementary Figures and Tables from A Ubiquitination Cascade Regulating the Integrated Stress Response and Survival in Carcinomas Open
Supplementary Figure S1 shows the strategy and result of co-essentiality module identificationfrom the DepMap CRISPR screen dataset and further characterization of the BIRC6 module. Supplementary Figure S2 shows the viability effect of BIR…
View article: Data from A Ubiquitination Cascade Regulating the Integrated Stress Response and Survival in Carcinomas
Data from A Ubiquitination Cascade Regulating the Integrated Stress Response and Survival in Carcinomas Open
Systematic identification of signaling pathways required for the fitness of cancer cells will facilitate the development of new cancer therapies. We used gene essentiality measurements in 1,086 cancer cell lines to identify selective coess…
View article: Data from A Ubiquitination Cascade Regulating the Integrated Stress Response and Survival in Carcinomas
Data from A Ubiquitination Cascade Regulating the Integrated Stress Response and Survival in Carcinomas Open
Systematic identification of signaling pathways required for the fitness of cancer cells will facilitate the development of new cancer therapies. We used gene essentiality measurements in 1,086 cancer cell lines to identify selective coess…
View article: Supplementary Figures and Tables from A Ubiquitination Cascade Regulating the Integrated Stress Response and Survival in Carcinomas
Supplementary Figures and Tables from A Ubiquitination Cascade Regulating the Integrated Stress Response and Survival in Carcinomas Open
Supplementary Figure S1 shows the strategy and result of co-essentiality module identificationfrom the DepMap CRISPR screen dataset and further characterization of the BIRC6 module. Supplementary Figure S2 shows the viability effect of BIR…
View article: Supplementary Figures S1-S6 from Cyclophosphamide-Mediated Tumor Priming for Enhanced Delivery and Antitumor Activity of HER2-Targeted Liposomal Doxorubicin (MM-302)
Supplementary Figures S1-S6 from Cyclophosphamide-Mediated Tumor Priming for Enhanced Delivery and Antitumor Activity of HER2-Targeted Liposomal Doxorubicin (MM-302) Open
Supplementary Figures S1-S6. Supplementary Fig. S1. The effect of cyclophosphamide on liposome delivery is dose dependent, requires a predose rather than a co-injection, and is not mediated by changes in blood clearance. Supplementary Fig.…
View article: Supplementary Tables 1-9 from CD36 Repression Activates a Multicellular Stromal Program Shared by High Mammographic Density and Tumor Tissues
Supplementary Tables 1-9 from CD36 Repression Activates a Multicellular Stromal Program Shared by High Mammographic Density and Tumor Tissues Open
PDF file - 392K, Tables S1, S2, S5, S6, S7 and S8: Patient information Table S3: LDAFs vs HDAFs microarray analysis Table S4: CD36 expression in published microarrays Table S9: Association of CD36 levels with tumor characteristics
View article: Supplementary Figure S5 from Selective Modulation of a Pan-Essential Protein as a Therapeutic Strategy in Cancer
Supplementary Figure S5 from Selective Modulation of a Pan-Essential Protein as a Therapeutic Strategy in Cancer Open
Differential NXT2 expression in neuroblastoma cell lines
View article: Supplementary Table S1 from Selective Modulation of a Pan-Essential Protein as a Therapeutic Strategy in Cancer
Supplementary Table S1 from Selective Modulation of a Pan-Essential Protein as a Therapeutic Strategy in Cancer Open
CRISPR guide sequences
View article: Supplementary Figure S3 from Selective Modulation of a Pan-Essential Protein as a Therapeutic Strategy in Cancer
Supplementary Figure S3 from Selective Modulation of a Pan-Essential Protein as a Therapeutic Strategy in Cancer Open
NXT2 loss leads to loss of NXF1
View article: Supplementary Figure S3 from Selective Modulation of a Pan-Essential Protein as a Therapeutic Strategy in Cancer
Supplementary Figure S3 from Selective Modulation of a Pan-Essential Protein as a Therapeutic Strategy in Cancer Open
NXT2 loss leads to loss of NXF1
View article: Supplementary Figures Legends 1-8, Table Legends 1-9, Methods from CD36 Repression Activates a Multicellular Stromal Program Shared by High Mammographic Density and Tumor Tissues
Supplementary Figures Legends 1-8, Table Legends 1-9, Methods from CD36 Repression Activates a Multicellular Stromal Program Shared by High Mammographic Density and Tumor Tissues Open
PDF file - 131K
View article: Supplementary Figures 1-8 from CD36 Repression Activates a Multicellular Stromal Program Shared by High Mammographic Density and Tumor Tissues
Supplementary Figures 1-8 from CD36 Repression Activates a Multicellular Stromal Program Shared by High Mammographic Density and Tumor Tissues Open
PDF file - 1.1MB, Figure S1: Image quantitation Figure S2: Histograms of Oil Red O quantitation in LDAFs and HDAFs Figure S3: Matrix protein immunofluorescent images of LDAFs and HDAFs Figure S4: Increased and decreased expression of CD36 …
View article: Data from CD36 Repression Activates a Multicellular Stromal Program Shared by High Mammographic Density and Tumor Tissues
Data from CD36 Repression Activates a Multicellular Stromal Program Shared by High Mammographic Density and Tumor Tissues Open
Although high mammographic density is considered one of the strongest risk factors for invasive breast cancer, the genes involved in modulating this clinical feature are unknown. Tissues of high mammographic density share key histologic fe…