Role of CAR and PXR in xenobiotic sensing and metabolism

YM Wang, SS Ong, SC Chai, T Chen - Expert opinion on drug …, 2012 - Taylor & Francis
Introduction: The xenobiotic detoxification system, which protects the human body from external
chemicals, comprises drug-metabolizing enzymes and transporters whose expressions …

Novel pyrrolopyrimidine-based α-helix mimetics: cell-permeable inhibitors of protein− protein interactions

JH Lee, Q Zhang, S Jo, SC Chai, M Oh… - Journal of the …, 2011 - ACS Publications
There is considerable interest in developing non-peptidic, small-molecule α-helix mimetics
to disrupt α-helix-mediated protein−protein interactions. Herein, we report the design of a …

[HTML][HTML] SPA70 is a potent antagonist of human pregnane X receptor

W Lin, YM Wang, SC Chai, L Lv, J Zheng, J Wu… - Nature …, 2017 - nature.com
Many drugs bind to and activate human pregnane X receptor (hPXR) to upregulate drug-metabolizing
enzymes, resulting in decreased drug efficacy and increased resistance. This …

Small-molecule modulators of PXR and CAR

SC Chai, MT Cherian, YM Wang, T Chen - Biochimica et Biophysica Acta …, 2016 - Elsevier
Two nuclear receptors, the pregnane X receptor (PXR) and the constitutive androstane receptor
(CAR), participate in the xenobiotic detoxification system by regulating the expression of …

[HTML][HTML] Blocking an N-terminal acetylation–dependent protein interaction inhibits an E3 ligase

…, D Bhasin, Y Chen, SS Ong, SC Chai… - Nature chemical …, 2017 - nature.com
N-terminal acetylation is an abundant modification influencing protein functions. Because ∼80%
of mammalian cytosolic proteins are N-terminally acetylated, this modification is …

Pregnane X receptor and drug-induced liver injury

YM Wang, SC Chai, CT Brewer… - Expert opinion on drug …, 2014 - Taylor & Francis
Introduction: The liver plays a central role in transforming and clearing foreign substances.
The continuous exposure of the liver to xenobiotics sometimes leads to impaired liver function…

Piperine activates human pregnane X receptor to induce the expression of cytochrome P450 3A4 and multidrug resistance protein 1

YM Wang, W Lin, SC Chai, J Wu, SS Ong… - Toxicology and applied …, 2013 - Elsevier
Activation of the pregnane X receptor (PXR) and subsequently its target genes, including those
encoding drug transporters and metabolizing enzymes, while playing substantial roles in …

A current structural perspective on PXR and CAR in drug metabolism

CD Buchman, SC Chai, T Chen - Expert opinion on drug …, 2018 - Taylor & Francis
Introduction: Pregnane X receptor (PXR) and the constitutive androstane receptor (CAR) are
two members of the nuclear receptor superfamily that play major roles in the expression of …

E3 ligase autoinhibition by C-degron mimicry maintains C-degron substrate fidelity

…, CT Gee, R Kalathur, J Li, N Purser, A Nourse, SC Chai… - Molecular Cell, 2023 - cell.com
E3 ligase recruitment of proteins containing terminal destabilizing motifs (degrons) is
emerging as a major form of regulation. How those E3s discriminate bona fide substrates from …

One protein, two enzymes revisited: a structural entropy switch interconverts the two isoforms of acireductone dioxygenase

T Ju, RB Goldsmith, SC Chai, MJ Maroney… - Journal of molecular …, 2006 - Elsevier
Acireductone dioxygenase (ARD) catalyzes different reactions between O 2 and 1,2-dihydroxy-3-oxo-5-(methylthio)pent-1-ene
(acireductone) depending upon the metal bound in the …