Setipiprant

Setipiprant (INN; developmental code names ACT-129968, KYTH-105) is an investigational drug developed for the treatment of asthma and scalp hair loss. It was originally developed by Actelion and acts as a selective, orally available antagonist of the prostaglandin D 2 receptor 2 (DP 2 ). The drug is being developed as a novel treatment for male pattern baldness by Allergan.

Setipiprant (INN; developmental code names ACT-129968, KYTH-105) is an investigational drug developed for the treatment of asthma and scalp hair loss. It was originally developed by Actelion and acts as a selective, orally available antagonist of the prostaglandin D 2 receptor 2 (DP 2 ). The drug is being developed as a novel treatment for male pattern baldness by Allergan. === Allergic conditions=== Setipiprant proved to be well tolerated and reasonably effective in reducing allergen-induced airway responses in asthmatic patient clinical trials. However, the drug, while supporting the concept that DP2 contributes to asthmatic disease, did not show sufficient advantage over existing drugs and was discontinued from further development for this application. ====Allergic conditions==== Setipiprant binds to the DP 2 receptor with a dissociation constant of 6 nM, representing potent antagonism of the receptor. The DP 2 receptor, also called the CRTh2 receptor, is a G-protein-coupled receptor (GPCR) that is expressed on certain inflammatory cells, such as eosinophils, basophils, and certain lymphocytes. For its mechanism of action in the treatment of allergic conditions, setipiprant's DP 2 antagonism prevents the action of prostaglandin D 2 (PGD 2 ) on these receptors. The DP 2 receptor mediates the activation of type 2 helper T (Th2) cells, eosinophils, and basophils in the lungs, which are white blood cells implicated in producing the inflammatory response the characterizes allergic conditions. Activation of DP 2 on Th2 cells by PGD 2 induces the secretion of inflammatory cytokines (interleukin (IL) 4, IL-5, and IL-13), which cause an increase of eosinophils in the blood, remodeling of lung tissue, and hypersensitivity of lung tissue to allergens. Setipiprant does not antagonize the thromboxane receptor (TP). The bronchoconstricting properties of PGD 2 are not inhibited by setipiprant, since these are mediated by the TP receptor. As a point of contrast, ramatroban is a selective TP antagonist and DP 2 receptor antagonist. Setipiprant does not appreciably inhibit the activity of the enzyme cyclooxygenase 1 (COX-1), which is responsible for the synthesis of prostaglandins (including PGD 2 ). ====Scalp hair loss==== Prostaglandin D2 synthase (PTGDS) is an enzyme that produces PGD 2 . In men with androgenic alopecia, the enzyme PTGDS is elevated in the bald scalp tissue, as well as its product PGD 2 . PGD 2 inhibits the growth of hair follicles through its activity on the DP 2 receptor, but not the DP 1 receptor. Theoretically, setipiprant's DP 2 receptor antagonism may counteract the activity of PGD 2 in hair follicles, thereby stimulating hair growth.

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