QS-21 is a purified soapbark tree (Quillaja saponaria) extract that enhances the ability of the immune system to respond to vaccine antigens. QS-21 is a promising adjuvant candidate for use in humans due to the ease of purification, its improved safety profile, and its ability to enhance cellular and humoral immunogenicity. The mechanism of action of QS-21 was speculated to be similar to QA, forming complexes with cholesterol that intercalate into the cell membrane lipids. This intercalation creates pores in the membrane to accelerate the uptake of a co-delivered antigen by the antigen presenting cells. Multiple clinical trials using QS-21 as an adjuvant, demonstrated satisfactory safety profiles and enhanced immunogenicity in immunocompromised volunteers

Linaclotide (marketed under the trade name Linzess and Constella) is a peptide agonist of the guanylate cyclase 2C (GC-C). Once linaclotide and its active metabolite binds to GC-C, it has local effect on the luminal surface of the intestinal epithelium. Activation of GC-C by linaclotide results in the intra- and extracellular increase of cyclic guanosine monophosphate concentrations (cGMP). This elevation of cGMP levels stimulates the secretion of chloride and bicarbonate into the intestinal lumen via activation of cystic fibrosis transmembrane conductance regulator (CFTR) ion channel. The metabolite of linaclotide MM-419447 (CCEYCCNPACTGC) contributes to the pharmacologic effects of linaclotide. Ultimately, linaclotide helps patients with IBS (especially with constipation) as GI transit is accelerated and the release of intestinal fluid is increased. In animal models, a decrease in visceral pain after administration of linaclotide may be observed. A decrease in the activity of pain-sensing nerves occurs as a result of an increase in extracellular cGMP. It was approved by the FDA in August 2012 for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation (IBS-C) in adults.