Kevin Dement

Learn More
Data from the clinical absolute bioavailability (F) study with cobimetinib suggested that F was lower than predicted based on its low hepatic extraction and good absorption. The CYP3A4 transgenic (Tg) mouse model with differential expression of CYP3A4 in the liver (Cyp3a(-/-)Tg-3A4Hep) or intestine (Cyp3a(-/-)Tg-3A4Int) and both liver and intestine(More)
Aliphatic nitrogen heterocycles such as piperazine, piperidine, pyrrolidine, morpholine, aziridine, azetidine, and azepane are well known building blocks in drug design and important core structures in approved drug therapies. These core units have been targets for metabolic attack by P450s and other drug metabolizing enzymes such as aldehyde oxidase and(More)
Bromo and extra terminal (BET) proteins (BRD2, BRD3, BRD4 and BRDT) are epigenetic transcriptional regulators required for efficient expression of growth promoting, cell cycle progression and antiapoptotic genes. Through their bromodomain, these proteins bind to acetylated lysine residues of histones and are recruited to transcriptionally active chromatin.(More)
Indoleamine and tryptophan 2,3-dioxygenases (IDO1 and TDO2) are pyrrolases catalyzing the oxidative cleavage of the 2,3-double bond of L-tryptophan in kynurenine pathway. In the tumor microenvironment, their increased activity prevents normal immune function, i.e. tumor cell recognition and elimination by cytotoxic T-cells. Consequently, inhibition of the(More)
s Evaluation of Cynomolgus Monkeys for the Identification of Endogenous Biomarkers for Hepatic Transporter Inhibition and as a Translatable Model to Predict Pharmacokinetic Interactions with Statins in Humans. Xiaoyan Chu, Shian-Jiun Shih, Rachel Shaw, Hannes Hentze, Grace H. Chan, Karen Owens, Shubing Wang, Xiaoxin Cai, Deborah Newton, Jose Castro-Perez,(More)
Data from the clinical absolute bioavailability (F) study with cobimetinib suggested that F was lower than predicted based on its low hepatic extraction and good absorption. The CYP3A4 transgenic (Tg) mouse model with differential expression of CYP3A4 in the liver (Cyp3aTg-3A4Hep) or intestine (Cyp3a Tg-3A4Int) and both liver and intestine(More)
Indoleamine 2, 3-dioxygenase (IDO1) is a cytosolic enzyme catalyzing the oxidation of tryptophan to kynur-enine. IDO1 plays an important role in modulating immune responses in cancer, where increasing evidence suggests that IDO1 expression by dendritic cells (DCs) and other antigen-presenting cells (APCs) contributes to tumor-mediated immune suppression.(More)
  • 1