... understood. In this review, we will provide an overview of the current status of selected small molecule ubiquitin system inhibitors. We will further discuss the unique challenges of targeting this ubiquitous and highly complex machinery, and explore and highlight potential ways in which these challenges...

... pathways and crucially, several members have been shown to be down-regulated in common cancers (such as breast and prostate). In the present study we focus on the development of lysine (K) acetyltransferase inhibitors (KATi) targeting the MYST family member Tip60 (Kat5), an essential protein, designed...

... on the available OGT inhibitors and summarizes advantages, limitations and future challenges. Recent advances in our understanding of the OGT catalytic mechanism have facilitated the rational design of competitive inhibitors. Novel compounds deriving from both OGT donor and acceptor substrate have been...

...′-triphosphate (ATP) inhibitor ligand pseudokinase tribbles tribbles 2 (TRIB2) Protein pseudokinases are components of essentially all sequenced kinomes and are defined as lacking at least one of the conserved amino acids that are required for efficient ATP binding and/or catalysis...

...-targeting tools are compared with protein-targeting tools with respect to their unique advantages and possible applications. 1 email [email protected] 7 7 2014 © The Authors Journal compilation © 2014 Biochemical Society 2014 chemical intervention tool inhibitor mimetic...

... inhibitor neuromodulator N -methyl- D -aspartate (NMDA) receptor regulation D -serine metabolism D -Serine plays a key role in crucial physiological processes such as brain development, neuronal cell migration, excitotoxicity, and learning and memory. It is critical for NMDAR activation...

... Biol. Ther. 2003 3 1133 1152 3 Arkin M.R. Wells J.A. Small-molecule inhibitors of protein–protein interactions: progressing towards the dream Nat. Rev. Drug Discov. 2004 3 301 317 4 Toogood P.L. Inhibition of protein–protein association by small molecules...

..., a chymotrypsin-like serine protease, is activated by a variety of apoptotic stimuli and is implicated in initiating internucleosomal DNA fragmentation. This occurs indirectly through the inactivation of LEI (leucocyte elastase inhibitor) via translational modification. Inhibition of AP24 is observed...

... and chymotrypsin using substrate-derived chloromethane inhibitors. One of the limitations of these inhibitors is that they irreversibly alkylate the active-site histidine residue which results in the oxyanion not being in the optimal position in the oxyanion hole. Substrate-derived glyoxal inhibitors...

...A.J. Bridges The development of kinase and phosphatase inhibitors as novel therapeutic agents has been stimulated by the discovery that most biological processes are controlled by the reversible phosphorylation of proteins. Most of the early results in this area were generated in oncology...

... and the phosphatidylinositol 3-phosphatase PTEN (phosphatase and tensin homologue deleted on chromosome 10). Specific inhibitors targeting phosphoinositide 3-kinase and protein phosphatases have been described and characterized, but no small-molecule tools for phosphoinositide phosphatases are currently available. The present...

... inhibitors. An imbalance between the active enzymes and their natural inhibitors leads to the accelerated destruction of connective tissue associated with the pathology of diseases such as arthritis, cancer, multiple sclerosis and cardiovascular diseases. The potential for using specific enzyme inhibitors...

... classes of tumoricidal agents that specifically target this elementary detoxification pathway in order to induce elevated concentrations of cytotoxic methylglyoxal in tumour cells. Special emphasis is placed on structure- and mechanism-based inhibitors of GlxI (glyoxalase I), the first enzyme...

... for the polyamines in cancer development, treatment and/or prevention. The recognition that polyamines are critical for the growth of cancer cells, and consequently the identification of their metabolic pathways as a target for therapeutic intervention, led to the development of a number of useful inhibitors...

...V. Dive; K. Lucet-Levannier; D. Georgiadis; J. Cotton; S. Vassiliou; P. Cuniasse; A. Yiotakis The development of the combinatorial chemistry of phosphinic peptides has led to the discovery of both highly potent and selective inhibitors of various zinc metalloproteinases. Several properties...