Matthew B. Boxer
National Institutes of Health
Publications 188
Phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) are important molecular players in a variety of diseases, such as cancer. Currently available PI5P4K inhibitors are reversible small molecules, which may lack selectivity and sufficient cellular on-target activity. In this study, we present a new class of covalent pan-PI5P4K inhibitors with potent biochemical and cellular activity. Our designs are based on THZ-P1-2, a covalent PI5P4K inhibitor previously developed in our lab. Here, we report f...
#1Sarah Wang (Dana Corporation)H-Index: 1
#2Elizabeth E. Hwang (Dana Corporation)H-Index: 1
Last.Brian D. Crompton (Dana Corporation)H-Index: 11
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Purpose: Ewing sarcoma is an aggressive solid tumor malignancy of childhood. Although current treatment regimens cure approximately 70% of patients with localized disease, they are ineffective for most patients with metastases or relapse. New treatment combinations are necessary for these patients. Experimental Design: Ewing sarcoma cells are dependent on focal adhesion kinase (FAK) for growth. To identify candidate treatment combinations for Ewing sarcoma, we performed a small-molecule library ...
2 CitationsSource
#1Xin Hu (NIH: National Institutes of Health)H-Index: 17
#2Yaqin Zhang (NIH: National Institutes of Health)H-Index: 8
Last.Min Shen (NIH: National Institutes of Health)H-Index: 42
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Classic Galactosemia is a potentially lethal autosomal recessive metabolic disorder caused by deficient galactose-1-phosphate uridyltransferase (GALT) that results in the buildup of galactose-1-phosphate (gal-1-p) in cells. Galactokinase (GALK1) is the enzyme responsible for converting galactose into gal-1-p. A pharmacological inhibitor of GALK1 is hypothesized to be therapeutic strategy for treating galactosemia by reducing production of gal-1-p. In this study, we report the discovery of novel ...
#1Sara E. Kearney (NIH: National Institutes of Health)H-Index: 1
#2Gergely Zahoránszky-Kőhalmi (NIH: National Institutes of Health)H-Index: 1
Last.Jason M. Rohde (NIH: National Institutes of Health)H-Index: 10
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Natural products and their derivatives continue to be wellsprings of nascent therapeutic potential. However, many laboratories have limited resources for biological evaluation, leaving their previously isolated or synthesized compounds largely or completely untested. To address this issue, the Canvass library of natural products was assembled, in collaboration with academic and industry researchers, for quantitative high-throughput screening (qHTS) across a diverse set of cell-based and biochemi...
5 CitationsSource
#1Jason M. Rohde (NIH: National Institutes of Health)H-Index: 10
#2Kyle R. Brimacombe (NIH: National Institutes of Health)H-Index: 17
Last.Matthew B. Boxer (NIH: National Institutes of Health)H-Index: 22
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Abstract Proliferating cells, including cancer cells, obtain serine both exogenously and via the metabolism of glucose. By catalyzing the first, rate-limiting step in the synthesis of serine from glucose, phosphoglycerate dehydrogenase (PHGDH) controls flux through the biosynthetic pathway for this important amino acid and represents a putative target in oncology. To discover inhibitors of PHGDH, a coupled biochemical assay was developed and optimized to enable high-throughput screening for inhi...
4 CitationsSource
#1Matthew B. BoxerH-Index: 22
#2Xiaodong WangH-Index: 1
Last.Min ShenH-Index: 9
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#1Daniel J. Urban (NIH: National Institutes of Health)H-Index: 20
#2Natalia J. Martinez (NIH: National Institutes of Health)H-Index: 5
Last.Matt Hall (NIH: National Institutes of Health)H-Index: 55
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Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are key metabolic enzymes that are mutated in a variety of cancers to confer a gain-of-function activity resulting in the accumulation of an oncometabolite, D-2-hydroxyglutarate (2-HG). Accumulation of 2-HG can result in epigenetic dysregulation and a block in cellular differentiation, suggesting these mutations play a role in neoplasia. Based on its potential as a cancer target, a number of small molecule inhibitors have been developed to specifi...
8 CitationsSource
#1Clemens Krepler (Wistar Institute)H-Index: 21
#2Katrin Sproesser (Wistar Institute)H-Index: 14
Last.Meenhard Herlyn (Wistar Institute)H-Index: 102
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Summary Therapy of advanced melanoma is changing dramatically. Following mutational and biological subclassification of this heterogeneous cancer, several targeted and immune therapies were approved and increased survival significantly. To facilitate further advancements through pre-clinical in vivo modeling, we have established 459 patient-derived xenografts (PDX) and live tissue samples from 384 patients representing the full spectrum of clinical, therapeutic, mutational, and biological hetero...
33 CitationsSource
#1Sui Seng TeeH-Index: 3
#2Jae Mo ParkH-Index: 3
Last.Daniel M. SpielmanH-Index: 42
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// Sui Seng Tee 1, 5, * , Jae Mo Park 1, 6, 7, * , Ralph E. Hurd 2 , Kyle R. Brimacombe 3, 4 , Matthew B. Boxer 3 , Tarik F. Massoud 1 , Brian K. Rutt 1 and Daniel M. Spielman 1 1 Department of Radiology, Stanford University, Stanford, CA, USA 2 Applied Sciences Laboratory, GE Healthcare, Menlo Park, CA, USA 3 National Center for Advancing Translational Sciences, NIH, Bethesda, MD, USA 4 NIH Chemical Genomics Center, Bethesda, MD, USA 5 Current/Present address: Memorial Sloan Kettering Cancer Ce...
5 CitationsSource
#1Brian D. CromptonH-Index: 11
#2Sarah WangH-Index: 1
Last.Kimberly StegmaierH-Index: 34
view all 14 authors...