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Articles 1 - 4 of 4
Full-Text Articles in Tissues
Yk-4-250, A Synthetic Telmisartan-Tempol Conjugate: Crystal Structure Of A Stabilized Free Radical Containing An Angiotensin At₁ Receptor Inhibitor, Simon Friedrich, Yali Kong, Faik N. Musayev, Milton L. Brown, B. Frank Gupton
Yk-4-250, A Synthetic Telmisartan-Tempol Conjugate: Crystal Structure Of A Stabilized Free Radical Containing An Angiotensin At₁ Receptor Inhibitor, Simon Friedrich, Yali Kong, Faik N. Musayev, Milton L. Brown, B. Frank Gupton
Department of Biomedical and Translational Sciences Faculty Publications
We report the first crystal structure of the telmisartan-tempol conjugate 2,2,6,6-tetramethyl-1-(λ'-oxidaneyl)piperidin-4-yl 4'-[(1,7'-dimethyl-2'-propyl-1H,3'H-[2,5'-bibenzo[d]imidazol]-3'-yl)methyl]-[1,1'-biphenyl]-2-carboxylate free radical (YK-4-250, C₄₂H₄₆N₅O₃), a dual-function inhibitor designed to target both the angiotensin II type 1 receptor (AT₁R) and reactive oxygen species (ROS). Structural analysis reveals a unique crystal architecture in which the nitroxide radical is stabilized within a sterically protected environment while preserving the telmisartan pharmacophore essential for high-affinity receptor antagonism. YK-4-250 is a novel small-molecule conjugate of telmisartan and tempol that incorporates a catalytic stabilized nitroxide radical and was rationally designed to mitigate gastrointestinal acute radiation syndrome (GI-ARS).
Yk-4-250 Mitigates Gastrointestinal Radiation Syndrome And Promotes Overall Survival Following Partial Body Radiation Injury, Vidya P. Kumar, Yali Kong, Kan Wang, Asa R. Britton-Jenkins, Stanton Dulan, Landon L. Moore, Debra Saunders, Randal May, Rheal Towner, Sanchita P. Ghosh, Courtney W. Houchen, Milton L. Brown
Yk-4-250 Mitigates Gastrointestinal Radiation Syndrome And Promotes Overall Survival Following Partial Body Radiation Injury, Vidya P. Kumar, Yali Kong, Kan Wang, Asa R. Britton-Jenkins, Stanton Dulan, Landon L. Moore, Debra Saunders, Randal May, Rheal Towner, Sanchita P. Ghosh, Courtney W. Houchen, Milton L. Brown
Department of Biomedical and Translational Sciences Faculty Publications
Acute gastrointestinal radiation syndrome (GI-ARS) is a significant health threat following high-dose ionizing radiation (IR) exposure, leading to severe morbidity and mortality. The syndrome is characterized by gastrointestinal tissue damage caused by angiotensin II (Ang II) and reactive oxygen species (ROS), resulting in impaired GI function, systemic bacteremia, multi-organ failure, and eventual death. Dysregulation of the renin-angiotensin system (RAS) via Ang II exacerbates ROS production through activation of the Angiotensin II type 1 receptor (AT1R). This underscores the need for agents capable of both scavenging ROS and inhibiting AT1R activity. To address this, we developed YK-4-250, a Tempol-conjugated angiotensin receptor …
P38 Mapk Is Involved In Epigenetic Regulation Of Fibrotic Genes In Replication Induced Senescence In Lung Fibroblasts, Shan Zhu, Jennifer Q. Zhou, Kan Wang, Ming-Lei Guo, Yan Sanders
P38 Mapk Is Involved In Epigenetic Regulation Of Fibrotic Genes In Replication Induced Senescence In Lung Fibroblasts, Shan Zhu, Jennifer Q. Zhou, Kan Wang, Ming-Lei Guo, Yan Sanders
Department of Biomedical and Translational Sciences Faculty Publications
Fibroblast activation is essential for tissue repair following injury; however, prolonged activation drives pathological fibrosis. Idiopathic pulmonary fibrosis (IPF), a progressive and age-associated lung disease, is characterized by aberrant fibroblast activation, with increasing evidence implicating senescent and near-senescent fibroblasts in its pathogenesis. However, the underlying mechanisms remain poorly defined. In this study, we investigated whether histone modification is involved in TGF-β1 treated lung fibroblasts and contributes to the fibrotic phenotype. Human IMR90 lung fibroblasts at low and high population doubling levels (LPDL and HPDL), as well as primary IPF fibroblasts, were used in this study. In response to TGF-β1, both …
Epigenetic Regulation In Fibrosis, Qingping Wei, Xiaoru Hu, Yan Sanders
Epigenetic Regulation In Fibrosis, Qingping Wei, Xiaoru Hu, Yan Sanders
Department of Biomedical and Translational Sciences Faculty Publications
[Introduction] Fibrosis is one of the pathological conditions underlying the progression of numerous chronic diseases, and it contributes substantially to morbidity and mortality worldwide. Increasing amounts of evidence indicate that epigenetic mechanisms—including DNA methylation, histone modifications, RNA modifications, and non-coding RNAs—play pivotal roles in epithelial cell injury and maladaptive tissue repair, inflammatory cell and fibroblast activation, and extracellular matrix remodeling and accumulation. Compared to genetic alterations, epigenetic changes are relatively reversible, positioning them as promising therapeutic targets. The articles collected in this Research Topic highlight recent advances in understanding how epigenetic regulation shapes fibrotic processes across multiple organ systems and …