Cornelissen, Jeremy C Obeng, Samuel Rice, Kenner C Zhang, Yan Negus, S Stevens Banks, Matthew L
Published in
The Journal of pharmacology and experimental therapeutics
Receptor theory predicts that fixed-proportion mixtures of a competitive, reversible agonist (e.g., fentanyl) and antagonist (e.g., naltrexone) at a common receptor [e.g., mu-opioid receptors (MORs)] will result in antagonist proportion-dependent decreases in apparent efficacy of the agonist/antagonist mixtures and downward shifts in mixture dose-e...
Vore, Mary
Published in
The Journal of pharmacology and experimental therapeutics
Burkey, Bryan F Hoglen, Niel C Inskeep, Philip Wyman, Margaret Hughes, Thomas E Vath, James E
Published in
The Journal of pharmacology and experimental therapeutics
Methionine aminopeptidase 2 (MetAP2) inhibition is a promising approach to treating diabetes, obesity, and associated metabolic disorders. Beloranib, a MetAP2 inhibitor previously investigated for treatment of Prader-Willi syndrome, was associated with venous thrombotic adverse events likely resulting from drug effects on vascular endothelial cells...
Cleator, John Wells, Christopher Dingus, Jane Kurtz, David T Hildebrandt, John D
Published in
The Journal of pharmacology and experimental therapeutics
Ser54 of Gsα binds guanine nucleotide and Mg2+ as part of a conserved sequence motif in GTP binding proteins. Mutating the homologous residue in small and heterotrimeric G proteins generates dominant negative proteins, but by protein-specific mechanisms. For αi/o this results from persistent binding of α to β γ, whereas for small GTP binding protei...
Lelievre, Benedicte Briet, Marie Godon, Charlotte Legras, Pierre Riou, Jeremie Vandeputte, Patrick Diquet, Bertrand Bouchara, Jean Philippe
Published in
The Journal of pharmacology and experimental therapeutics
Cerebral Scedosporium infections usually occur in lung transplant recipients as well as in immunocompetent patients in the context of near-drowning. Voriconazole is the first-line treatment. The diffusion of voriconazole through the blood-brain barriers in the context of cerebral infection and cyclosporine administration is crucial and remains a ma...
Shin, Niu Li, Yun-Long Mei, Song Wang, Kathy He Hall, Leslie Katiyar, Kamna Wang, Qian Yang, Gengjie Rumberger, Beth Leffet, Lynn
...
Published in
The Journal of pharmacology and experimental therapeutics
Phosphatidylinositol 3-kinase delta (PI3Kδ) is a critical signaling molecule in B cells and is considered a target for development of therapies against various B cell malignancies. INCB040093 is a novel PI3Kδ small-molecule inhibitor and has demonstrated promising efficacy in patients with Hodgkin's lymphoma in clinical studies. In this study, we d...
Kyte, S Lauren Toma, Wisam Bagdas, Deniz Meade, Julie A Schurman, Lesley D Lichtman, Aron H Chen, Zhi-Jian Del Fabbro, Egidio Fang, Xianjun Bigbee, John W
...
Published in
The Journal of pharmacology and experimental therapeutics
Chemotherapy-induced peripheral neuropathy (CIPN), a consequence of peripheral nerve fiber dysfunction or degeneration, continues to be a dose-limiting and debilitating side effect during and/or after cancer chemotherapy. Paclitaxel, a taxane commonly used to treat breast, lung, and ovarian cancers, causes CIPN in 59-78% of cancer patients. Novel i...
Whyte-Allman, Sana-Kay Hoque, Md Tozammel Jenabian, Mohammad-Ali Routy, Jean-Pierre Bendayan, Reina
Published in
The Journal of pharmacology and experimental therapeutics
Poor antiretroviral drug (ARV) penetration in the testes could be due, in part, to the presence of ATP-binding cassette (ABC) membrane-associated drug efflux transporters such as P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug resistance-associated proteins (MRPs) expressed at the blood-testis barrier (BTB). The functi...
Corboz, Michel R Li, Zhili Malinin, Vladimir Plaunt, Adam J Konicek, Donna M Leifer, Franziska G Chen, Kuan-Ju Laurent, Charles E Yin, Han Biernat, Marzena C
...
Published in
The Journal of pharmacology and experimental therapeutics
This article describes the preclinical pharmacology and pharmacokinetics (PK) of hexadecyl-treprostinil (C16TR), a prodrug of treprostinil (TRE), formulated in a lipid nanoparticle (LNP) for inhalation as a pulmonary vasodilator. C16TR showed no activity (>10 µM) in receptor binding and enzyme inhibition assays, including binding to prostaglandin E...
Leonard, Michael Z Alapafuja, Shakiru O Ji, Lipin Shukla, Vidyanand G Liu, Yingpeng Nikas, Spyros P Makriyannis, Alexandros Bergman, Jack Kangas, Brian D
Published in
The Journal of pharmacology and experimental therapeutics
An improved understanding of the endocannabinoid system has provided new avenues of drug discovery and development toward the management of pain and other behavioral maladies. Exogenous cannabinoid type 1 (CB1) receptor agonists such as Δ9-tetrahydrocannabinol are increasingly used for their medicinal actions; however, their utility is constrained ...
