A5023925299- Endoplasmic Reticulum Stress and Disease
- Cancer, Hypoxia, and Metabolism
- RNA modifications and cancer
- Genetics and Neurodevelopmental Disorders
- Glutathione Transferases and Polymorphisms
- Advanced Drug Delivery Systems
- Protein Degradation and Inhibitors
- Enzyme function and inhibition
- Autophagy in Disease and Therapy
- Ubiquitin and proteasome pathways
- Genomics, phytochemicals, and oxidative stress
- Calcium signaling and nucleotide metabolism
- ATP Synthase and ATPases Research
- Genetics, Aging, and Longevity in Model Organisms
- Pluripotent Stem Cells Research
- Magnetic properties of thin films
- Drug Solubulity and Delivery Systems
- Adenosine and Purinergic Signaling
- Pancreatic and Hepatic Oncology Research
- Mitochondrial Function and Pathology
- Iron oxide chemistry and applications
- Advanced biosensing and bioanalysis techniques
- PI3K/AKT/mTOR signaling in cancer
- Analytical Chemistry and Chromatography
- Cytokine Signaling Pathways and Interactions
University of Michigan
2019-2023
Tsinghua University
2015
Fuzhou University
2014
Academy of Military Medical Sciences
2012
University of Colorado System
2011
Institute of Basic Medical Sciences of the Chinese Academy of Medical Sciences
2010
United States Government Accountability Office
2005
Second Military Medical University
2001
Abstract GRP78 (glucose-regulated protein, 78 kDa) is a key regulator of endoplasmic reticulum (ER) stress signaling. Cancer cells are highly proliferative and have high demand for protein synthesis folding, which results in significant on the ER. To respond to ER maintain cellular homeostasis, activate unfolded response (UPR) that promotes either survival or apoptotic death. utilize UPR promote growth. In this study, we describe discovery series novel hydroxyquinoline inhibitors. A...
Targeting oxidative phosphorylation (OXPHOS) complexes is an emerging strategy to disrupt the metabolism of select cancer subtypes and overcome resistance targeted therapies. Here, we describe our lead optimization campaign on a series benzene-1,4-disulfonamides as novel OXPHOS complex I inhibitors. This effort led discovery compound 23 (DX3-213B) one most potent inhibitors reported date. DX3-213B disrupts adenosine triphosphate (ATP) generation, inhibits function, results in growth...
Inhibition of oxidative phosphorylation (OXPHOS) is a promising therapeutic strategy for select cancers that are dependent on aerobic metabolism. Here, we report the discovery, optimization, and structure–activity relationship (SAR) study series novel OXPHOS inhibitors. The hit compound, benzene-1,4-disulfonamide 1, was discovered in phenotypic screen selective cytotoxicity galactose-containing medium. Our multi-parameter optimization campaign led to discovery 65 (DX3-235), showing nanomolar...
Using reported glutathione S-transferase omega 1 (GSTO1-1) cocrystal structures, we designed and synthesized acrylamide-containing compounds that covalently bind to Cys32 on the catalytic site. Starting from a thiazole derivative 10 (GSTO1-1 IC50 = 0.6 μM), compound 18 was cocrystallized with GSTO1. Modification amide moiety of hit significantly increased GSTO1-1 inhibitory potency. We solved structures new derivatives, 37 44, bearing an side chain bound These showed reorientation phenyl...
Disulfide bond formation is a critical post-translational modification of newly synthesized polypeptides in the oxidizing environment endoplasmic reticulum and mediated by protein disulfide isomerase (PDIA1). In this study, we report series α-aminobenzylphenol analogues as potent PDI inhibitors. The lead compound,
Pancreatic cancer cells adapt to nutrient-scarce metabolic conditions by increasing their oxidative phosphorylation reserve survive. Here, we present a first-in-class small-molecule NDUFS7 antagonist that inhibits (OXPHOS) for the treatment of pancreatic cancer. The lead compound, DX2-201, suppresses proliferation panel cell lines, and metabolically stable analogue, DX3-213B, shows significant efficacy in syngeneic model Exome sequencing six out clones resistant DX2-201 revealed pV91M...
nanozerovalent iron particles coated with biopolymer nanoskin were prepared by liquid phase method. For a period of time, the remaining xanthan layer can prevent oxidation nanoiron in air. The goal this study is to demonstrate that magnetic properties fluid which suspend xanthan/guar fluid. Magnetic hysteresis loops measured at room temperatures and field-cooled / zero-field-cooled magnetization curves obtained low temperature vibrating sample magnetometer. results interpret did not strongly...
<div>Abstract<p>GRP78 (glucose-regulated protein, 78 kDa) is a key regulator of endoplasmic reticulum (ER) stress signaling. Cancer cells are highly proliferative and have high demand for protein synthesis folding, which results in significant on the ER. To respond to ER maintain cellular homeostasis, activate unfolded response (UPR) that promotes either survival or apoptotic death. utilize UPR promote growth. In this study, we describe discovery series novel hydroxyquinoline...
<p>Supplementary materials include detailed chemistry, supplementary and methods, references, figures.</p>
<div>Abstract<p>GRP78 (glucose-regulated protein, 78 kDa) is a key regulator of endoplasmic reticulum (ER) stress signaling. Cancer cells are highly proliferative and have high demand for protein synthesis folding, which results in significant on the ER. To respond to ER maintain cellular homeostasis, activate unfolded response (UPR) that promotes either survival or apoptotic death. utilize UPR promote growth. In this study, we describe discovery series novel hydroxyquinoline...
<p>Supplementary materials include detailed chemistry, supplementary and methods, references, figures.</p>