Results 81 to 90 of about 743,371 (240)

Discovery, Design, and Optimization of Isoxazole Azepine BET Inhibitors

, 2016
The identification of a novel series of small molecule BET inhibitors is described. Using crystallographic binding modes of an amino-isoxazole fragment and known BET inhibitors, a structure-based drug design effort lead to a novel isoxazole azepine ...
Brian K. Albrecht (1417963), Shivangi Joshi (1398922), Florence Poy (240698), Jean-Christophe Harmange (1398934), Yves Leblanc (1398952), Christopher G. Nasveschuk (334912), Rishi G. Vaswani (1398928), Nandana Bangalore Srinivasamurthy (1912945), Eneida Pardo (1398916), James E. Audia (1398949), Sreegouri Yellapantula (1912942), Victor S. Gehling (1398931), Alexandre Côté (1398955), Barbara M. Bryant (1912939), Swarnakumari Birudukota (1912951), Louise Bergeron (1417939), Steve Bellon (1398937), Robert J. Sims (1417966), Michael C. Hewitt (1912948), Hariharan Jayaram (1417942), Jennifer A. Mertz (1417945), Ravichandran Sankaranarayanan (1912954), Peter Sandy (235034), Alexander M. Taylor (1398943)   +23 more
core   +1 more source

Autophagy and mitophagy in pancreatic β‐cell homeostasis and their involvement in diabetes pathophysiology

FEBS Letters, EarlyView.
This review focuses on the role of autophagy and mitophagy in maintaining pancreatic β‐cell function and homeostasis. We discuss how genetic defects affecting these pathways contribute to the development of type 1, type 2, monogenic, and gestational diabetes. We further explore their potential as therapeutic targets. Created in BioRender.
Yunkyeong Lee, Mingming Tong, Anna L. Gloyn   +2 more
wiley   +1 more source

Partial depletion of plasminogen activator inhibitor‐1 decreases subcutaneous fat cell hypertrophy and liver cholesterol in high‐fat‐fed female mice

FEBS Letters, EarlyView.
Obesity raises blood levels of PAI‐1, a protein linked to metabolic dysfunction‐associated steatotic liver disease in people with obesity. In female mice fed a high‐fat diet, partially lowering PAI‐1 led to smaller subcutaneous fat cells and lower liver cholesterol, without changing body weight or insulin sensitivity.
Claudia E. Ramirez Bustamante, Robert Sharp, Pradip K. Saha, Elizabeth S. Anaya, Elizabeth L. Lieu, Evelyn L. de Groot, Pooja Patel, Mi Jeong Heo, Aaron R. Cox, Kang Ho Kim, Sean M. Hartig   +10 more
wiley   +1 more source

Inducible In Vivo Silencing of Brd4 Identifies Potential Toxicities of Sustained BET Protein Inhibition

Cell Reports, 2014
BET family proteins are novel therapeutic targets for cancer and inflammation and represent the first chromatin readers against which small-molecule inhibitors have been developed.
Jessica E. Bolden, Nilgun Tasdemir, Lukas E. Dow, Johan H. van Es, John E. Wilkinson, Zhen Zhao, Hans Clevers, Scott W. Lowe   +7 more
doaj   +1 more source

Bromodomain Inhibitors as Therapeutics for Herpesvirus-Related Disease: All BETs Are Off?

Frontiers in Cellular and Infection Microbiology, 2020
Although the ubiquitous human herpesviruses (HHVs) are rarely associated with serious disease of the healthy host, primary infection and reactivation in immunocompromised individuals can lead to significant morbidity and, in some cases, mortality ...
Ian J. Groves, John H. Sinclair, Mark R. Wills   +2 more
doaj   +1 more source

Chemical probes and inhibitors of bromodomains outside the BET family [PDF]

, 2016
In the last five years, the development of inhibitors of bromodomains has emerged as an area of intensive worldwide research. Emerging evidence has implicated a number of non-BET bromodomains in the onset and progression of diseases such as cancer, HIV ...
Hay, Duncan A., Clark, Peter G.K., Brennan, Paul E., Moustakim, Moses, Dixon, Darren J.   +4 more
core   +1 more source

Structures of mycobacterial 3‐methylcrotonyl‐CoA carboxylase reveal carrier‐domain translocation between catalytic sites

FEBS Letters, EarlyView.
Mycobacterial 3‐methylcrotonyl‐CoA carboxylase uses a mobile biotin‐carrying domain to shuttle a carboxyl group between two catalytic sites, enabling carboxylation of 3‐methylcrotonyl‐CoA during leucine breakdown. Cryo‐electron microscopy captures the carrier at both sites and reveals an inward loop movement that may prevent futile rebinding to the ...
Ajit Yadav, Bogdan I. Florea, Sebastian Geibel   +2 more
wiley   +1 more source

BET Bromodomain Inhibition Promotes Anti-tumor Immunity by Suppressing PD-L1 Expression

Cell Reports, 2016
Restoration of anti-tumor immunity by blocking PD-L1 signaling through the use of antibodies has proven to be beneficial in cancer therapy. Here, we show that BET bromodomain inhibition suppresses PD-L1 expression and limits tumor progression in ovarian ...
Hengrui Zhu, Fee Bengsch, Nikolaos Svoronos, Melanie R. Rutkowski, Benjamin G. Bitler, Michael J. Allegrezza, Yuhki Yokoyama, Andrew V. Kossenkov, James E. Bradner, Jose R. Conejo-Garcia, Rugang Zhang   +10 more
doaj   +1 more source

The heterodimeric amino acid transporters (HAT) of the SLC7/SLC3 family: A structure−function relationships and relevance to human pathology

FEBS Letters, EarlyView.
Heterodimeric amino acid transporters consist of SLC7 and SLC3 family proteins arranged in a conserved structural organization. They regulate nutrient transport across cell membranes, supporting essential cellular functions. These transporters also contribute to xenobiotic/drug uptake and distribution.
Mariafrancesca Scalise, Tiziano Mazza, Raffaella Scanga, Lara Console, Michele Galluccio, Cesare Indiveri   +5 more
wiley   +1 more source

BET inhibitors as potential anticancer agents

, 2015
In human cancers, epigenetic alterations such as DNA methylation and histone modifications can play a key role in the dysregulation of gene expression leading to the silencing of tumor suppressor genes or to the overexpression of proto-oncogenes.
Griguolo, G., Stathis, A.
core   +1 more source