Kevin Dement

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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)
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)
Background Progressive hypertension and deteriorating renal function are hallmarks of cardio-renal syndromes. Historically, the deoxycorticosterone acetate (DOCA)-salt model has been used to assess the therapeutic potential of antihypertensives in the setting of low renin and volume-dependent hypertension. Dahl-salt-sensitive (Dahl-SS) rats represent a(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)
Improved anti-tumor immunity and efficacy upon combination of the IDO1 inhibitor GDC-0919 with anti-PD-l1 blockade versus anti-PD-l1 alone in preclinical tumor models Jessica Spahn, Jing Peng, Edward Lorenzana, David Kan, Thomas Hunsaker, Ehud Segal, Mario Mautino, Erik Brincks, Andrea Pirzkall, Sean Kelley, Sami Mahrus, Liling Liu, Stephanie Dale, Cristine(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)
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)
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