Darrin D. Stuart
YOU?
Author Swipe
View article: Supplementary Tables1 from STX-721, a Covalent EGFR/HER2 Exon 20 Inhibitor, Utilizes Exon 20–Mutant Dynamic Protein States and Achieves Unique Mutant Selectivity Across Human Cancer Models
Supplementary Tables1 from STX-721, a Covalent EGFR/HER2 Exon 20 Inhibitor, Utilizes Exon 20–Mutant Dynamic Protein States and Achieves Unique Mutant Selectivity Across Human Cancer Models Open
Supplementary Tables S1 through S7
View article: Supplementary Methods1 from STX-721, a Covalent EGFR/HER2 Exon 20 Inhibitor, Utilizes Exon 20–Mutant Dynamic Protein States and Achieves Unique Mutant Selectivity Across Human Cancer Models
Supplementary Methods1 from STX-721, a Covalent EGFR/HER2 Exon 20 Inhibitor, Utilizes Exon 20–Mutant Dynamic Protein States and Achieves Unique Mutant Selectivity Across Human Cancer Models Open
Methods and method references related to crystallography and molecular dynamics
View article: Supplementary Figures1 from STX-721, a Covalent EGFR/HER2 Exon 20 Inhibitor, Utilizes Exon 20–Mutant Dynamic Protein States and Achieves Unique Mutant Selectivity Across Human Cancer Models
Supplementary Figures1 from STX-721, a Covalent EGFR/HER2 Exon 20 Inhibitor, Utilizes Exon 20–Mutant Dynamic Protein States and Achieves Unique Mutant Selectivity Across Human Cancer Models Open
Supplementary Figures S1-S6
View article: Data from STX-721, a Covalent EGFR/HER2 Exon 20 Inhibitor, Utilizes Exon 20–Mutant Dynamic Protein States and Achieves Unique Mutant Selectivity Across Human Cancer Models
Data from STX-721, a Covalent EGFR/HER2 Exon 20 Inhibitor, Utilizes Exon 20–Mutant Dynamic Protein States and Achieves Unique Mutant Selectivity Across Human Cancer Models Open
Purpose:Commonly occurring oncogenic mutations in EGFR render non–small cell lung cancers sensitive to approved EGFR-targeted drugs. EGFR in-frame exon 20 insertion (ex20ins) mutants are, however, less sensitive to such drugs. The efficacy…
View article: STX-721, a Covalent EGFR/HER2 Exon 20 Inhibitor, Utilizes Exon 20–Mutant Dynamic Protein States and Achieves Unique Mutant Selectivity Across Human Cancer Models
STX-721, a Covalent EGFR/HER2 Exon 20 Inhibitor, Utilizes Exon 20–Mutant Dynamic Protein States and Achieves Unique Mutant Selectivity Across Human Cancer Models Open
Purpose: Commonly occurring oncogenic mutations in EGFR render non–small cell lung cancers sensitive to approved EGFR-targeted drugs. EGFR in-frame exon 20 insertion (ex20ins) mutants are, however, less sensitive to such drugs. The efficac…
View article: Discovery of STX-721, a Covalent, Potent, and Highly Mutant-Selective EGFR/HER2 Exon20 Insertion Inhibitor for the Treatment of Non-Small Cell Lung Cancer
Discovery of STX-721, a Covalent, Potent, and Highly Mutant-Selective EGFR/HER2 Exon20 Insertion Inhibitor for the Treatment of Non-Small Cell Lung Cancer Open
After L858R and ex19del epidermal growth factor receptor (EGFR) mutations, ex20ins mutations are the third most common class of driver-mutations in non-small cell lung cancer (NSCLC). Unfortunately, first-, second-, and third-generation EG…
View article: Figure 3 from STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts
Figure 3 from STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts Open
The effect of STX-478 and alpelisib on glucose homeostasis. A, Tumor-naive female BALB/c nude mice were dosed for 5 days as indicated (n = 5/group) and subjected to an ITT. On day 5, animals were fasted for 6 hours and dosed with drug by o…
View article: Figure 6 from STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts
Figure 6 from STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts Open
STX-478 combination therapies in ER+ breast cancer models with fulvestrant and palbociclib. A, T47D xenograft tumors were established in female NOD scid gamma immunodeficient (NSG) mice. When tumors reached approximately 200 mm3, mice were…
View article: Figure 6 from STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts
Figure 6 from STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts Open
STX-478 combination therapies in ER+ breast cancer models with fulvestrant and palbociclib. A, T47D xenograft tumors were established in female NOD scid gamma immunodeficient (NSG) mice. When tumors reached approximately 200 mm3, mice were…
View article: Figure 5 from STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts
Figure 5 from STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts Open
The efficacy of STX-478 is similar or superior to high-dose alpelisib across PI3Kα-mutant tumor xenografts while sparing insulin resistance (p.o., oral administration; q.d., daily). A, Final tumor volume percent change is represented for G…
View article: Figure 1 from STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts
Figure 1 from STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts Open
STX-478 binds a novel allosteric site on PI3Kα and achieves mutant selectivity through differential binding kinetics. A, The molecular structure of STX-478. B, Inhibition of enzyme activities of WT PI3Kα as well as kinase-domain and helica…
View article: Figure 2 from STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts
Figure 2 from STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts Open
Assessment of STX-478 mutant selectivity by profiling target engagement and functional activity in cellular assays. A, pAKT inhibition dose–response curves (HTRF assay) in MCF10A isogenic cell lines. B, Representative pAKT inhibition dose–…
View article: Figure 1 from STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts
Figure 1 from STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts Open
STX-478 binds a novel allosteric site on PI3Kα and achieves mutant selectivity through differential binding kinetics. A, The molecular structure of STX-478. B, Inhibition of enzyme activities of WT PI3Kα as well as kinase-domain and helica…
View article: Supplementary Tables and Figures from STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts
Supplementary Tables and Figures from STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts Open
Includes Supplementary Tables S1 - S4 and Supplementary Figures S1 - S6
View article: Figure 2 from STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts
Figure 2 from STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts Open
Assessment of STX-478 mutant selectivity by profiling target engagement and functional activity in cellular assays. A, pAKT inhibition dose–response curves (HTRF assay) in MCF10A isogenic cell lines. B, Representative pAKT inhibition dose–…
View article: Figure 4 from STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts
Figure 4 from STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts Open
Efficacy and PK/PD profiling of STX-478 and alpelisib in CAL-33 xenograft tumors. A and B, CAL-33 xenograft tumors were established in female BALB/c nude mice. Animals were randomized into treatment groups (n = 6) at approximately 160 mm3 …
View article: Data from STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts
Data from STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts Open
Phosphoinositide 3-kinase α (PIK3CA) is one of the most mutated genes across cancers, especially breast, gynecologic, and head and neck squamous cell carcinoma tumors. Mutations occur throughout the gene, but hotspot mutations in the helic…
View article: Figure 3 from STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts
Figure 3 from STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts Open
The effect of STX-478 and alpelisib on glucose homeostasis. A, Tumor-naive female BALB/c nude mice were dosed for 5 days as indicated (n = 5/group) and subjected to an ITT. On day 5, animals were fasted for 6 hours and dosed with drug by o…
View article: Figure 4 from STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts
Figure 4 from STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts Open
Efficacy and PK/PD profiling of STX-478 and alpelisib in CAL-33 xenograft tumors. A and B, CAL-33 xenograft tumors were established in female BALB/c nude mice. Animals were randomized into treatment groups (n = 6) at approximately 160 mm3 …
View article: Figure 5 from STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts
Figure 5 from STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts Open
The efficacy of STX-478 is similar or superior to high-dose alpelisib across PI3Kα-mutant tumor xenografts while sparing insulin resistance (p.o., oral administration; q.d., daily). A, Final tumor volume percent change is represented for G…
View article: Supplementary Tables and Figures from STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts
Supplementary Tables and Figures from STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts Open
Includes Supplementary Tables S1 - S4 and Supplementary Figures S1 - S6
View article: Data from STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts
Data from STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts Open
Phosphoinositide 3-kinase α (PIK3CA) is one of the most mutated genes across cancers, especially breast, gynecologic, and head and neck squamous cell carcinoma tumors. Mutations occur throughout the gene, but hotspot mutations in the helic…
View article: Precision Oncology Comes of Age: Designing Best-in-Class Small Molecules by Integrating Two Decades of Advances in Chemistry, Target Biology, and Data Science
Precision Oncology Comes of Age: Designing Best-in-Class Small Molecules by Integrating Two Decades of Advances in Chemistry, Target Biology, and Data Science Open
Small-molecule drugs have enabled the practice of precision oncology for genetically defined patient populations since the first approval of imatinib in 2001. Scientific and technology advances over this 20-year period have driven the evol…
View article: STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts
STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts Open
Phosphoinositide 3-kinase α (PIK3CA) is one of the most mutated genes across cancers, especially breast, gynecologic, and head and neck squamous cell carcinoma tumors. Mutations occur throughout the gene, but hotspot mutations in the helic…
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: Supplementary Figures 1-3 from The Novel Oral Hsp90 Inhibitor NVP-HSP990 Exhibits Potent and Broad-spectrum Antitumor Activities <i>In Vitro</i> and <i>In Vivo</i>
Supplementary Figures 1-3 from The Novel Oral Hsp90 Inhibitor NVP-HSP990 Exhibits Potent and Broad-spectrum Antitumor Activities <i>In Vitro</i> and <i>In Vivo</i> Open
PDF file - 212K
View article: Figure S1 from Distinct Transcriptional Programming Drive Response to MAPK Inhibition in <i>BRAF</i><sup>V600</sup>-Mutant Melanoma Patient-Derived Xenografts
Figure S1 from Distinct Transcriptional Programming Drive Response to MAPK Inhibition in <i>BRAF</i><sup>V600</sup>-Mutant Melanoma Patient-Derived Xenografts Open
Response to encorafenib and binimetinib of BRAFV600 mutant melanoma PDX models.
View article: Supplemental Figure S3 from RAF-Mutant Melanomas Differentially Depend on ERK2 Over ERK1 to Support Aberrant MAPK Pathway Activation and Cell Proliferation
Supplemental Figure S3 from RAF-Mutant Melanomas Differentially Depend on ERK2 Over ERK1 to Support Aberrant MAPK Pathway Activation and Cell Proliferation Open
Supplementary Figure S3 shows overexpression of MAPK1 (ERK2) in human melanoma cell lines compared to MAPK3 (ERK1) and cell lines of other lineages, a correlation of ERK2 dependency with MAPK1 (ERK2) mRNA expression, and ERK1/2 protein exp…
View article: Data from Allele-Specific Mechanisms of Activation of MEK1 Mutants Determine Their Properties
Data from Allele-Specific Mechanisms of Activation of MEK1 Mutants Determine Their Properties Open
Mutations at multiple sites in MEK1 occur in cancer, suggesting that their mechanisms of activation might be different. We analyzed 17 tumor-associated MEK1 mutants and found that they drove ERK signaling autonomously or in a RAS/RAF-depen…
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…