Accessible proteins in normal tissue

Accessible proteins in normal tissue refers to the collective group of proteins expressed on the surface of or within the extracellular matrix of healthy, non-diseased cells that are reachable by systemically administered therapeutic agents (Uhlén et al., 2015). This concept is critical in the development of targeted therapies, such as antibody-drug conjugates (ADCs) and T-cell engagers, where binding to these proteins in healthy organs leads to "on-target, off-tumor" toxicity (Human Protein Atlas). Understanding the distribution and expression levels of these proteins across different organs helps in predicting the safety profile and therapeutic window of a drug. High expression of a target protein in normal tissue often precludes its use as a therapeutic target due to the risk of severe adverse effects. Consequently, drug discovery efforts prioritize targets with high differential expression between diseased and normal tissues to minimize interactions with this broad class of accessible proteins. Databases such as the Human Protein Atlas provide comprehensive maps of these proteins to help researchers avoid targets with high normal tissue accessibility (Thul et al., 2017). Understanding this "accessible proteome" is also vital for predicting the "sink effect," where a drug is sequestered by healthy tissues, reducing its availability at the intended disease site. Therefore, while not a therapeutic target itself, this category represents the primary hurdle in achieving high specificity in precision medicine.

Other names

Normal tissue proteomeOff-target antigensHealthy tissue surfaceomeNon-target tissue proteins

Not applicable; this is a broad category of proteins rather than a specific drug target.