Utility of non-human primates in drug development: Comparison of non-human primate and human drug-metabolizing cytochrome P450 enzymes

Y Uno, S Uehara, H Yamazaki - Biochemical pharmacology, 2016 - Elsevier
Cynomolgus monkeys (Macaca fascicularis, an Old World Monkey) have been widely used
as a non-human primate model in preclinical studies because of their genetic and …

[HTML][HTML] An improved TK-NOG mouse as a novel platform for humanized liver that overcomes limitations in both male and female animals

S Uehara, Y Higuchi, N Yoneda, K Kawai… - Drug Metabolism and …, 2022 - Elsevier
We developed a novel immunodeficient NOG mouse expressing HSVtk mutant clone 30
cDNA under the control of mouse transthyretin gene enhancer/promoter (NOG-TKm30) to …

In Vivo and In Vitro Induction of Cytochrome P450 3A4 by Thalidomide in Humanized-Liver Mice and Experimental Human Hepatocyte HepaSH cells

S Uehara, N Murayama, Y Higuchi… - Chemical Research …, 2024 - ACS Publications
Autoinduction of cytochrome P450 (P450) 3A4-mediated metabolism of thalidomide was
investigated in humanized-liver mice and human hepatocyte-derived HepaSH cells. The mean …

Immunochemical detection of cytochrome P450 enzymes in liver microsomes of 27 cynomolgus monkeys

S Uehara, N Murayama, Y Nakanishi, DC Zeldin… - … of Pharmacology and …, 2011 - ASPET
The cynomolgus monkey is widely used as a primate model in preclinical studies because
of its evolutionary closeness to humans. Despite their importance in drug metabolism, the …

[HTML][HTML] Humanized liver TK-NOG mice with functional deletion of hepatic murine cytochrome P450s as a model for studying human drug metabolism

S Uehara, Y Iida, M Ida-Tanaka, M Goto, K Kawai… - Scientific Reports, 2022 - nature.com
Chimeric TK-NOG mice with a humanized liver (normal Hu-liver) are a unique animal model
for predicting drug metabolism in humans. However, residual mouse hepatocytes …

[HTML][HTML] HepaSH cells: Experimental human hepatocytes with lesser inter-individual variation and more sustainable availability than primary human hepatocytes

S Uehara, Y Higuchi, N Yoneda, R Ito… - Biochemical and …, 2023 - Elsevier
Primary human hepatocytes (PHHs) have been commonly used as the gold standard in many
drug metabolism studies, regardless of having large inter-individual variation. These inter-…

Genetic variants of CYP3A4 and CYP3A5 in cynomolgus and rhesus macaques

Y Uno, A Matsushita, N Osada, S Uehara… - Drug metabolism and …, 2010 - ASPET
Cynomolgus and rhesus macaques are frequently used in preclinical trials due to their close
evolutionary relationships to humans. We conducted an initial screening for genetic variants …

Newly identified tree shrew cytochrome P450 2B6 (CYP2B6) and pig CYP2B6b are functional drug-metabolising enzymes

Y Uno, G Ushirozako, S Uehara, N Murayama… - Xenobiotica, 2022 - Taylor & Francis
Tree shrews have high phylogenetic affinity to humans and are used in various fields of
biomedical research, especially hepatitis virus infection; however, cytochromes P450 (P450s or …

Novel marmoset cytochrome P450 2C19 in livers efficiently metabolizes human P450 2C9 and 2C19 substrates, S-warfarin, tolbutamide, flurbiprofen, and omeprazole

S Uehara, Y Uno, T Inoue, M Kawano, M Shimizu… - Drug metabolism and …, 2015 - ASPET
The common marmoset (Callithrix jacchus), a small New World monkey, has the potential
for use in human drug development due to its evolutionary closeness to humans. Four novel …

Cytochrome P450-dependent drug oxidation activities and their expression levels in liver microsomes of chimeric TK-NOG mice with humanized livers

S Uehara, N Yoneda, Y Higuchi, H Yamazaki… - Drug Metabolism and …, 2022 - Elsevier
Hepatic cytochrome P450 (P450)-dependent drug oxidation activity has not been completely
characterized in chimeric TK-NOG mice with humanized livers (humanized liver mice). In …