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View article: Supplementary Material and Methods from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers
Supplementary Material and Methods from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers Open
Supplementary Material and Methods. File contains the following: Transcriptome sequencing and analysis, Soft agar assay, 2D and 3D Cell proliferation screen and compound characterization information.
View article: Figure S3 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers
Figure S3 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers Open
(A) In vivo primary human colorectal xenograft model HCOX4087 treated with trametinib (0.3 mg/kg QD), SHP099 (100 mg/kg QD), and a pan-RTK inhibitor, Dovitinib (100 mg/kg QD). (B-C) In vivo efficacy of selective VEGFR2 inhibitor, BFH772 (3…
View article: Table S2 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers
Table S2 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers Open
Supplementary Table 2: List of all cell lines in the CCLE where sensitivity to SHP099 was evaluated in 2D. Lineage and genetic status of KRAS and BRAF are shown. Blank cells represent cell line data where genetic or screening data do not e…
View article: Data from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers
Data from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers Open
KRAS, an oncogene mutated in nearly one third of human cancers, remains a pharmacologic challenge for direct inhibition except for recent advances in selective inhibitors targeting the G12C variant. Here, we report that selective in…
View article: Table S4 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers
Table S4 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers Open
Supplementary Table 4: List of cell lines evaluated for sensitivity to SHP099 (Tab 1) or an RTK-inhibitor (Tab 2) in 2D or 3D. Included is the lineage and the KRAS mutation status. Where data are blank, no viable data was available, or the…
View article: Supplementary Material and Methods from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers
Supplementary Material and Methods from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers Open
Supplementary Material and Methods. File contains the following: Transcriptome sequencing and analysis, Soft agar assay, 2D and 3D Cell proliferation screen and compound characterization information.
View article: Figure S2 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers
Figure S2 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers Open
In vivo efficacy of SHP099 (100 mg/kg, daily) in the KYSE-520 esophageal cancer cell line model. Data are plotted as the treatment mean {plus minus} s.e.m (n=7) ( (B-I) In vivo efficacy data for cell line models represented in Fig. 3E. SHP…
View article: Table S1 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers
Table S1 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers Open
Supplementary Table 1: List of all cell lines in the CCLE (Cancer Cell Line Encyclopedia) where sensitivity to SHP2 (PTPN11) knockdown was evaluated in 2D. Lineage, and genetic status of KRAS and BRAF are shown. Blank cells represent cell …
View article: Table S4 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers
Table S4 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers Open
Supplementary Table 4: List of cell lines evaluated for sensitivity to SHP099 (Tab 1) or an RTK-inhibitor (Tab 2) in 2D or 3D. Included is the lineage and the KRAS mutation status. Where data are blank, no viable data was available, or the…
View article: Table S3 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers
Table S3 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers Open
Supplementary Table 3: A total of 246 cell lines were evaluated for both SHP2 knockdown and SHP099 sensitivity. Data displays PTPN11 shRNA ATARIS Quantile Score and SHP099 IC50 and Amax for each cell line tested.
View article: Figure S3 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers
Figure S3 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers Open
(A) In vivo primary human colorectal xenograft model HCOX4087 treated with trametinib (0.3 mg/kg QD), SHP099 (100 mg/kg QD), and a pan-RTK inhibitor, Dovitinib (100 mg/kg QD). (B-C) In vivo efficacy of selective VEGFR2 inhibitor, BFH772 (3…
View article: Table S2 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers
Table S2 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers Open
Supplementary Table 2: List of all cell lines in the CCLE where sensitivity to SHP099 was evaluated in 2D. Lineage and genetic status of KRAS and BRAF are shown. Blank cells represent cell line data where genetic or screening data do not e…
View article: Fig S1 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers
Fig S1 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers Open
(A) Effects of SHP099 and erlotinib on proliferation of EGFR-dependent and RAS/RAF wildtype Detroit-562 and KYSE520 cells grown in 2D monolayer or 3D spheroids (with 20% matrigel) for 6 days. The colored dotted lines at the bottom of graph…
View article: Fig S1 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers
Fig S1 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers Open
(A) Effects of SHP099 and erlotinib on proliferation of EGFR-dependent and RAS/RAF wildtype Detroit-562 and KYSE520 cells grown in 2D monolayer or 3D spheroids (with 20% matrigel) for 6 days. The colored dotted lines at the bottom of graph…
View article: Table S1 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers
Table S1 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers Open
Supplementary Table 1: List of all cell lines in the CCLE (Cancer Cell Line Encyclopedia) where sensitivity to SHP2 (PTPN11) knockdown was evaluated in 2D. Lineage, and genetic status of KRAS and BRAF are shown. Blank cells represent cell …
View article: Figure S4 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers
Figure S4 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers Open
(A) Immunoblot of p-RSK3 and qPCR for DUSP6 from MIA PaCa-2 xenografts collected 3 hours after the last dose from Fig 5C. (B) Immunoblot for the designated proteins from MIA PaCa-2 cells grown in 2D, 3D and from in vivo xenografts without …
View article: Figure S4 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers
Figure S4 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers Open
(A) Immunoblot of p-RSK3 and qPCR for DUSP6 from MIA PaCa-2 xenografts collected 3 hours after the last dose from Fig 5C. (B) Immunoblot for the designated proteins from MIA PaCa-2 cells grown in 2D, 3D and from in vivo xenografts without …
View article: Figure S2 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers
Figure S2 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers Open
In vivo efficacy of SHP099 (100 mg/kg, daily) in the KYSE-520 esophageal cancer cell line model. Data are plotted as the treatment mean {plus minus} s.e.m (n=7) ( (B-I) In vivo efficacy data for cell line models represented in Fig. 3E. SHP…
View article: Data from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers
Data from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers Open
KRAS, an oncogene mutated in nearly one third of human cancers, remains a pharmacologic challenge for direct inhibition except for recent advances in selective inhibitors targeting the G12C variant. Here, we report that selective in…
View article: Table S3 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers
Table S3 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers Open
Supplementary Table 3: A total of 246 cell lines were evaluated for both SHP2 knockdown and SHP099 sensitivity. Data displays PTPN11 shRNA ATARIS Quantile Score and SHP099 IC50 and Amax for each cell line tested.
View article: Supplementary Figures 1 - 6 from IDH1 Mutations Alter Citric Acid Cycle Metabolism and Increase Dependence on Oxidative Mitochondrial Metabolism
Supplementary Figures 1 - 6 from IDH1 Mutations Alter Citric Acid Cycle Metabolism and Increase Dependence on Oxidative Mitochondrial Metabolism Open
PDF file - 348KB, Figure S1: Isogenic IDH1 mutation compromises metabolic reprogramming under hypoxia. Figure S2: Simulated and measured uncorrected MIDs. Figure S3: Compromised Reductive TCA Metabolism is specific to cells with mutant IDH…
View article: Supplementary Methods, Figure Legends from IDH1 Mutations Alter Citric Acid Cycle Metabolism and Increase Dependence on Oxidative Mitochondrial Metabolism
Supplementary Methods, Figure Legends from IDH1 Mutations Alter Citric Acid Cycle Metabolism and Increase Dependence on Oxidative Mitochondrial Metabolism Open
PDF file - 136KB
View article: Supplementary Methods, Figure Legends from IDH1 Mutations Alter Citric Acid Cycle Metabolism and Increase Dependence on Oxidative Mitochondrial Metabolism
Supplementary Methods, Figure Legends from IDH1 Mutations Alter Citric Acid Cycle Metabolism and Increase Dependence on Oxidative Mitochondrial Metabolism Open
PDF file - 136KB
View article: Data from IDH1 Mutations Alter Citric Acid Cycle Metabolism and Increase Dependence on Oxidative Mitochondrial Metabolism
Data from IDH1 Mutations Alter Citric Acid Cycle Metabolism and Increase Dependence on Oxidative Mitochondrial Metabolism Open
Oncogenic mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) occur in several types of cancer, but the metabolic consequences of these genetic changes are not fully understood. In this study, we performed 13C metabolic flux …
View article: Supplementary Figures 1 - 6 from IDH1 Mutations Alter Citric Acid Cycle Metabolism and Increase Dependence on Oxidative Mitochondrial Metabolism
Supplementary Figures 1 - 6 from IDH1 Mutations Alter Citric Acid Cycle Metabolism and Increase Dependence on Oxidative Mitochondrial Metabolism Open
PDF file - 348KB, Figure S1: Isogenic IDH1 mutation compromises metabolic reprogramming under hypoxia. Figure S2: Simulated and measured uncorrected MIDs. Figure S3: Compromised Reductive TCA Metabolism is specific to cells with mutant IDH…
View article: Data from IDH1 Mutations Alter Citric Acid Cycle Metabolism and Increase Dependence on Oxidative Mitochondrial Metabolism
Data from IDH1 Mutations Alter Citric Acid Cycle Metabolism and Increase Dependence on Oxidative Mitochondrial Metabolism Open
Oncogenic mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) occur in several types of cancer, but the metabolic consequences of these genetic changes are not fully understood. In this study, we performed 13C metabolic flux …
View article: Supplementary Tables 1 - 4 from IDH1 Mutations Alter Citric Acid Cycle Metabolism and Increase Dependence on Oxidative Mitochondrial Metabolism
Supplementary Tables 1 - 4 from IDH1 Mutations Alter Citric Acid Cycle Metabolism and Increase Dependence on Oxidative Mitochondrial Metabolism Open
PDF file - 93KB, Estimates Fluxes for HCT116 Parental and IDH1 R132H/+ 2H1 cells under Normoxia and Hypoxia (2 percent Oxygen).
View article: Supplementary Tables 1 - 4 from IDH1 Mutations Alter Citric Acid Cycle Metabolism and Increase Dependence on Oxidative Mitochondrial Metabolism
Supplementary Tables 1 - 4 from IDH1 Mutations Alter Citric Acid Cycle Metabolism and Increase Dependence on Oxidative Mitochondrial Metabolism Open
PDF file - 93KB, Estimates Fluxes for HCT116 Parental and IDH1 R132H/+ 2H1 cells under Normoxia and Hypoxia (2 percent Oxygen).
View article: SHP2 blockade enhances anti-tumor immunity via tumor cell intrinsic and extrinsic mechanisms
SHP2 blockade enhances anti-tumor immunity via tumor cell intrinsic and extrinsic mechanisms Open
SHP2 is a ubiquitous tyrosine phosphatase involved in regulating both tumor and immune cell signaling. In this study, we discovered a novel immune modulatory function of SHP2. Targeting this protein with allosteric SHP2 inhibitors promoted…
View article: Identification of TNO155, an Allosteric SHP2 Inhibitor for the Treatment of Cancer
Identification of TNO155, an Allosteric SHP2 Inhibitor for the Treatment of Cancer Open
SHP2 is a nonreceptor protein tyrosine phosphatase encoded by the PTPN11 gene and is involved in cell growth and differentiation via the MAPK signaling pathway. SHP2 also plays an important role in the programed cell death pathway (…