Abnormal proteins

Abnormal proteins represent a diverse class of therapeutic targets characterized by pathological structural changes or genetic mutations that result in cellular dysfunction and disease. This category includes misfolded proteins and aggregates such as amyloid-beta and alpha-synuclein associated with neurodegeneration, as well as mutated oncogenic proteins like BCR-ABL and KRAS in cancer [1, 2, 10]. These entities are often targeted through various pharmacological approaches, including monoclonal antibodies for aggregate clearance and small molecule inhibitors that selectively bind to mutated active sites [3, 5, 12]. Recent advancements have also introduced targeted protein degradation (TPD), which utilizes bifunctional molecules like PROTACs or molecular glues to facilitate the destruction of pathogenic proteins by the cell's own quality control machinery [8, 9, 13]. A critical challenge in targeting abnormal proteins is the requirement for high molecular specificity to distinguish between the disease-causing variant and its essential, wild-type counterpart in healthy tissues [3, 11].

Other names

Misfolded proteinsAberrant proteinsMutant proteinsPathogenic protein aggregatesProteotoxic species

Drugs targeting abnormal proteins utilize mechanisms such as selective inhibition of mutated signaling nodes, antibody-mediated clearance of extracellular aggregates, and targeted protein degradation via proteasomal or lysosomal pathways.