Inhibitors of sickling.

A number of agents that prevent sickling in vitro have been discovered during the past decade. In general, such agents act directly on the hemoglobin S tetramer to inhibit gelation or alter oxygen affinity. Most currently recognized agents lack specificity for hemoglobin and modify other cellular constituents. Synthesis of reagents such as the bifunctional aspirin derivative, bis (3,5-dibromosalicyl) fumarate, with increased specificity for hemoglobin, represents a rational approach to the design of new therapeutic agents for sickle cell anemia. Membrane active agents such as cetiedil inhibit sickling in vitro but have not yet been shown to be effective in vivo. Reduction in the intracellular concentration of hemoglobin S apparently may reduce the frequency of painful crises but is difficult to achieve with current techniques. Although no antisickling therapy can yet be described as both safe and effective, the outlook for the future seems promising because of the large number of agents under active investigation.