Inherited mutations in the rod visual pigment, rhodopsin, cause the degenerative blinding
condition, retinitis pigmentosa (RP). Over 150 different mutations in rhodopsin have been …

The unfolded protein response (UPR) is a homeostatic mechanism by which cells regulate
levels of misfolded proteins in the endoplasmic reticulum (ER). Although it is well …

The ATPase valosin-containing protein (VCP)/p97 has emerged as a central and important
element of the ubiquitin system. Together with a network of cofactors, it regulates an ever …

Protein folding is a complex, error-prone process that often results in an irreparable protein
by-product. These by-products can be recognized by cellular quality control machineries …

The cellular mechanisms underlying hereditary photoreceptor degeneration are still poorly
understood, a problem that is exacerbated by the enormous genetic heterogeneity of this …

Misfolded proteins compromise cellular homeostasis. This is especially problematic in the
endoplasmic reticulum (ER), which is a high-capacity protein-folding compartment and …

Unfolded protein response (UPR) of the endoplasmic reticulum (UPRER) helps maintain
proteostasis in the cell. The ability to mount an effective UPRER to external stress (iUPRER) …

The endoplasmic reticulum (ER) is the primary intracellular organelle responsible for protein
and lipid biosynthesis, protein folding and trafficking, calcium homeostasis, and several …

Retinal degenerations are a group of clinically and genetically heterogeneous disorders
characterised by progressive loss of vision due to neurodegeneration. The retina is a highly …

To discover more potent p97 inhibitors, we carried out a structure–activity relationship study
of the quinazoline scaffold previously identified from our HTS campaigns. Two improved …