Human serum albumin (HSA) - Sudlow's site II (HSA Site IIIA)

Human serum albumin (HSA) is the most abundant protein in human blood plasma, serving as a vital transport vehicle for a wide range of endogenous and exogenous compounds [1, 12]. Site IIIA, also known as Sudlow's site II, is one of the two primary drug-binding regions located within subdomain IIIA of the protein's heart-shaped structure [1, 4]. This site specifically accommodates small, aromatic carboxylic acids and neutral molecules, including many non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and benzodiazepines like diazepam [4, 8]. Beyond its role in drug transport, HSA is essential for maintaining the oncotic pressure of blood and buffering plasma pH [1, 9]. In clinical practice, the binding affinity at Site IIIA significantly influences the pharmacokinetic profile, half-life, and volume of distribution of therapeutic agents [2, 5]. Alterations in albumin levels or competition for Site IIIA can lead to significant drug-drug interactions and changes in the concentration of free, pharmacologically active drugs [2, 14]. Consequently, HSA is a critical consideration in drug development and serves as a target for albumin-based drug delivery systems [5, 15].

Other names

Sudlow's site IISubdomain IIIAHSA Site IIIbuprofen binding site

Reversible binding and transport of ligands; modulation of free drug concentration; drug delivery vehicle