Eastman, Clifford L Fender, Jason S Klein, Pavel D'Ambrosio, Raimondo
Published in
The Journal of pharmacology and experimental therapeutics
Mounting evidence suggests the synaptic vesicle glycoprotein 2A (SV2A) targeted by levetiracetam may contribute to epileptogenesis. Levetiracetam has shown anti-inflammatory, antioxidant, neuroprotective and possible antiepileptogenic effects in brain injury and seizure/epilepsy models, and a phase 2 study has signaled a possible clinical antiepile...
Willette, Robert N Mangrolia, Parth Pondell, Stephen M Lee, Christopher Young Woo Yoo, Sanghee Rudoltz, Marc S Cowen, Benjamin R Welsch, Dean J
Published in
The Journal of pharmacology and experimental therapeutics
Metabolic reprogramming of the myofibroblast plays a fundamental role in the pathogenesis of fibrosing interstitial lung diseases. Here, we characterized the in vitro and in vivo metabolic and anti-fibrotic effects of IM156, an oxidative phosphorylation (OXPHOS) modulator that acts by inhibiting Protein Complex 1 (PC1). In vitro, IM156 inhibited TG...
Gresch, Anne Noguera Hurtado, Héctor Wörmeyer, Laura De Luca, Vivien Wiggers, Rebekka Seebohm, Guiscard Wünsch, Bernhard Düfer, Martina
Published in
The Journal of pharmacology and experimental therapeutics
Participation of NMDA receptors (NMDARs) in the failure of pancreatic beta cells during development of type 2 diabetes mellitus is discussed. Our study investigates whether beta cell mass and function can be preserved by selectively addressing the GluN2B subunit of the NMDAR. NMDAR activation by NMDA and its co-agonist glycine moderately influenced...
Youngblood, Beth Li, Kevin Gehlert, Donald R Medina, Julio C Schwartz, Neil
Published in
The Journal of pharmacology and experimental therapeutics
Opioid use disorder (OUD) is a major socioeconomic burden. An ideal OUD pharmacotherapy will mitigate the suffering associated with opioid-withdrawal, inhibit the effects of high efficacy opioids, and minimize opioid-cravings while being safe and accessible to a diverse patient population. Although current OUD pharmacotherapies inhibit the euphoric...
Lin, Qingxiang Qian, Zhicheng Jusko, William J Mager, Donald E Ma, Wen Wee Straubinger, Robert M
Published in
The Journal of pharmacology and experimental therapeutics
Median survival of pancreatic ductal adenocarcinoma cancer (PDAC) is 6 months, with 9% 5-year survival. Standard-of-care gemcitabine (Gem) provides only modest survival benefits, and combination therapies integrating novel targeted agents could improve outcomes. Fibroblast growth factor (FGF) receptors (FGFRs) play important roles in PDAC growth an...
Zhu, Wei Shyr, Zeenat A Lo, Donald C Zheng, Wei
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...
Wallman, Mikael Scheuerer, Stefan Martel, Eric Pairet, Nicolas Jirstrand, Mats Gabrielsson, Johan
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...
Hosoda, Ryusuke Hamada, Hiroki Uesugi, Daisuke Iwahara, Naotoshi Nojima, Iyori Horio, Yoshiyuki Kuno, Atsushi
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...
Ronaldson, Patrick T Brzica, Hrvoje Abdullahi, Wazir Reilly, Bianca G Davis, Thomas P
Published in
The Journal of pharmacology and experimental therapeutics
Our in vivo rodent studies have shown that organic anion transporting polypeptide (Oatp) 1a4 is critical for blood-to-brain transport of statins, drugs that are effective neuroprotectants. Additionally, transforming growth factor-β (TGF-β) signaling via the activin receptor-like kinase 1 (ALK1) receptor regulates Oatp1a4 functional expression. The ...
Zhang, Guolin Zhang, Chi Sun, Jia'ao Xiong, Yongjian Wang, Liang Chen, Dapeng
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...
