Published in The Journal of pharmacology and experimental therapeutics
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to be a global threat since its emergence. Although several COVID-19 vaccines have become available, the prospective timeframe for achieving effective levels of vaccination across global populations remains uncertain. Moreover, the e...
Published in The Journal of pharmacology and experimental therapeutics
Cardiovascular adverse effects in drug development are a major source of compound attrition. Characterization of blood pressure (BP), heart rate (HR), stroke volume (SV), and QT-interval prolongation are therefore necessary in early discovery. It is, however, common practice to analyze these effects independently of each other. High-resolution time...
Published in The Journal of pharmacology and experimental therapeutics
Resveratrol affords protection against reactive oxygen species (ROS)-related diseases via activation of SIRT1, an NAD+-dependent deacetylase. However, the low bioavailability of resveratrol limits its therapeutic applications. Since piceatannol is a hydroxyl analog of resveratrol with higher bioavailability, it could be an alternative to resveratro...
Published in The Journal of pharmacology and experimental therapeutics
Recent studies suggest an important role for RNA, especially non-coding RNA, in inflammatory bowel disease (IBD) and colon cancer. Drug development based on regulating RNA rather than protein is a promising new area. Phytochemicals are naturally occurring plant-derived compounds with chemical diversity, biological activity, easy availability, and l...
Published in The Journal of pharmacology and experimental therapeutics
Immune checkpoint inhibitors have emerged as a frontline treatment of a variety of malignancies. However, only a subset of patients respond to these therapies, and many initial responders eventually develop resistance, leading to tumor relapse. Programmed death protein 1 is one of the checkpoint inhibitors that is expressed on activated T cells and...
Published in The Journal of pharmacology and experimental therapeutics
Constitutively active extracellular signal-regulated kinase (ERK1/2) signaling promotes cancer cell proliferation and survival. We previously described a class of compounds containing a 1,1-dioxido-2,5-dihydrothiophen-3-yl 4-benzenesulfonate scaffold that targeted ERK2 substrate docking sites and selectively inhibited ERK1/2-dependent functions, in...
Published in The Journal of pharmacology and experimental therapeutics
Pulmonary fibrosis remains a serious biomedical problem with no cure and an urgent need for better therapies. Neuraminidases (NEUs), including NEU1, have been recently implicated in the mechanism of pulmonary fibrosis by us and others. We now have tested the ability of a broad-spectrum neuraminidase inhibitor, DANA, to modulate the in vivo response...
Published in The Journal of pharmacology and experimental therapeutics
P-glycoprotein (P-gp) is a major blood-brain barrier (BBB) efflux transporter. In vitro approaches, including bi-directional efflux ratio (ER), are used to measure P-gp-mediated transport, but findings can be inconsistent across models. We propose a novel, more physiologically relevant, in vitro model: uni-directional apical efflux ratio (AP-ER) - ...
Published in The Journal of pharmacology and experimental therapeutics
Histidine-rich glycoprotein (HRG) treatment ameliorated the survival rate of septic mice by suppressing excess immunothrombus formation. Although such findings suggested that HRG may be one of the most useful drugs for sepsis, obtaining a stable experimental system to standardize the HRG drug product is difficult to achieve using neutrophils isolat...
Published in The Journal of pharmacology and experimental therapeutics
ONO-4641 is a second-generation sphingosine 1-phosphate (S1P) receptor modulator that exhibits selectivity for S1P receptors 1 and 5. Treatment with ONO-4641 leads to a reduction in magnetic resonance imaging disease measures in patients with relapsing-remitting multiple sclerosis. The objective of this study was to explore the potential impact of ...
