Names | |
---|---|
IUPAC name 9α,15S-Dihydroxy-11-oxo-prosta-5Z,13E-dien-1-oic acid | |
Identifiers | |
3D model (JSmol) | |
ChEBI | |
ChemSpider | |
ECHA InfoCard | 100.164.741 |
KEGG | |
MeSH | Prostaglandin+D2 |
PubChem CID | |
UNII | |
CompTox Dashboard (EPA) | |
| |
| |
Properties | |
C20H32O5 | |
Molar mass | 352.471 g·mol−1 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). |
Prostaglandin D2 (or PGD2) is a prostaglandin that binds to the receptor PTGDR (DP1), as well as CRTH2 (DP2). [1] [2] It is a major prostaglandin produced by mast cells – recruits Th2 cells, eosinophils, and basophils. In mammalian organs, large amounts of PGD2 are found only in the brain and in mast cells. It is critical to development of allergic diseases such as asthma. Research carried out in 1989 [3] found PGD2 is the primary mediator of vasodilation (the "niacin flush") after ingestion of niacin (nicotinic acid).
A 2012 research paper indicates a causal link between elevated levels of localized PGD2 and hair growth inhibition. [4] Applied topically, the researchers found PGD2 prevents hair growth, and mice that were genetically inclined to produce higher levels of PGD2 had inhibited hair growth. The researchers also found PGD2 levels were much higher in balding scalp tissue than nonbalding scalp tissue, through increased levels of prostaglandin D2 synthase. The paper suggested that inhibition of hair growth involved binding of PGD2 to a DP2 receptor, and that DP2 therefore would be a therapeutic target for androgenic alopecia in both men and women with hair loss and thinning. [5] Because PGD2's relation to asthma has been known for several years, several drugs that seek to reduce the effect of PGD2 through blocking the DP2 are already in clinical trials. [5]
In silico simulations have predicted the following as potential inhibitors of PGD2 synthase: [12]
Prostaglandins (PG) are a group of physiologically active lipid compounds called eicosanoids that have diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are derived enzymatically from the fatty acid arachidonic acid. Every prostaglandin contains 20 carbon atoms, including a 5-carbon ring. They are a subclass of eicosanoids and of the prostanoid class of fatty acid derivatives.
Alopecia areata, also known as spot baldness, is a condition in which hair is lost from some or all areas of the body. It often results in a few bald spots on the scalp, each about the size of a coin. Psychological stress and illness are possible factors in bringing on alopecia areata in individuals at risk, but in most cases there is no obvious trigger. People are generally otherwise healthy. In a few cases, all the hair on the scalp is lost, or all body hair is lost. Hair loss can be permanent, or temporary.
Minoxidil is a medication used for the treatment of high blood pressure and pattern hair loss. It is an antihypertensive and a vasodilator. It is available as a generic medication by prescription in oral tablet form and over the counter as a topical liquid or foam.
Eicosanoids are signaling molecules made by the enzymatic or non-enzymatic oxidation of arachidonic acid or other polyunsaturated fatty acids (PUFAs) that are, similar to arachidonic acid, around 20 carbon units in length. Eicosanoids are a sub-category of oxylipins, i.e. oxidized fatty acids of diverse carbon units in length, and are distinguished from other oxylipins by their overwhelming importance as cell signaling molecules. Eicosanoids function in diverse physiological systems and pathological processes such as: mounting or inhibiting inflammation, allergy, fever and other immune responses; regulating the abortion of pregnancy and normal childbirth; contributing to the perception of pain; regulating cell growth; controlling blood pressure; and modulating the regional flow of blood to tissues. In performing these roles, eicosanoids most often act as autocrine signaling agents to impact their cells of origin or as paracrine signaling agents to impact cells in the proximity of their cells of origin. Some eicosanoids, such as prostaglandins, may also have endocrine roles as hormones to influence the function of distant cells.
Finasteride, sold under the brand names Proscar and Propecia among others, is a medication used to treat pattern hair loss and benign prostatic hyperplasia (BPH) in men. It can also be used to treat excessive hair growth in women. It is usually taken orally but there are topical formulations for patients with hair loss, designed to minimize systemic exposure by acting specifically on hair follicles.
The management of hair loss, includes prevention and treatment of alopecia, baldness, and hair thinning, and regrowth of hair.
Pattern hair loss is a hair loss condition that primarily affects the top and front of the scalp. In male-pattern hair loss (MPHL), the hair loss typically presents itself as either a receding front hairline, loss of hair on the crown and vertex of the scalp, or a combination of both. Female-pattern hair loss (FPHL) typically presents as a diffuse thinning of the hair across the entire scalp.
A prostaglandin antagonist is a hormone antagonist acting upon one or more prostaglandins, a subclass of eicosanoid compounds which function as signaling molecules in numerous types of animal tissues.
Most of the eicosanoid receptors are integral membrane protein G protein-coupled receptors (GPCRs) that bind and respond to eicosanoid signaling molecules. Eicosanoids are rapidly metabolized to inactive products and therefore are short-lived. Accordingly, the eicosanoid-receptor interaction is typically limited to a local interaction: cells, upon stimulation, metabolize arachidonic acid to an eicosanoid which then binds cognate receptors on either its parent cell or on nearby cells to trigger functional responses within a restricted tissue area, e.g. an inflammatory response to an invading pathogen. In some cases, however, the synthesized eicosanoid travels through the blood to trigger systemic or coordinated tissue responses, e.g. prostaglandin (PG) E2 released locally travels to the hypothalamus to trigger a febrile reaction. An example of a non-GPCR receptor that binds many eicosanoids is the PPAR-γ nuclear receptor.
Prostaglandin receptors or prostanoid receptors represent a sub-class of cell surface membrane receptors that are regarded as the primary receptors for one or more of the classical, naturally occurring prostanoids viz., prostaglandin D2,, PGE2, PGF2alpha, prostacyclin (PGI2), thromboxane A2 (TXA2), and PGH2. They are named based on the prostanoid to which they preferentially bind and respond, e.g. the receptor responsive to PGI2 at lower concentrations than any other prostanoid is named the Prostacyclin receptor (IP). One exception to this rule is the receptor for thromboxane A2 (TP) which binds and responds to PGH2 and TXA2 equally well.
The prostaglandin D2 receptor 1 (DP1), a G protein-coupled receptor encoded by the PTGDR gene (also termed PTGDR1), is primarily a receptor for prostaglandin D2 (PGD2). The receptor is a member of the prostaglandin receptors belonging to the subfamily A14 of rhodopsin-like receptors. Activation of DP1 by PGD2 or other cognate receptor ligands is associated with a variety of physiological and pathological responses in animal models.
Prostaglandin-H2 D-isomerase (PTGDS) is an enzyme that in humans is encoded by the PTGDS gene.
Cyclopentenone prostaglandins are a subset of prostaglandins (PGs) or prostanoids that has 15-deoxy-Δ12,14-prostaglandin J2 (15-d-Δ12,14-PGJ2), Δ12-PGJ2, and PGJ2 as its most prominent members but also including PGA2, PGA1, and, while not classified as such, other PGs. 15-d-Δ12,14-PGJ2, Δ12-PGJ2, and PGJ2 share a common mono-unsaturated cyclopentenone structure as well as a set of similar biological activities including the ability to suppress inflammation responses and the growth as well as survival of cells, particularly those of cancerous or neurological origin. Consequently, these three cyclopentenone-PGs and the two epoxyisoprostanes are suggested to be models for the development of novel anti-inflammatory and anti-cancer drugs. The cyclopenentone prostaglandins are structurally and functionally related to a subset of isoprostanes viz., two cyclopentenone isoprostanes, 5,6-epoxyisoprostane E2 and 5,6-epoxisoprostane A2.
In enzymology, a prostaglandin-D synthase is an enzyme that catalyzes the chemical reaction
Prostaglandin D2 receptor 2 (DP2 or CRTH2) is a human protein encoded by the PTGDR2 gene. DP2 has also been designated as CD294 (cluster of differentiation 294). It is a member of the class of prostaglandin receptors which bind with and respond to various prostaglandins. DP2 along with prostaglandin DP1 receptor are receptors for prostglandin D2 (PGD2). Activation of DP2 by PGD2 or other cognate receptor ligands has been associated with certain physiological and pathological responses, particularly those associated with allergy and inflammation, in animal models and certain human diseases.
Prostaglandin F receptor (FP) is a receptor belonging to the prostaglandin (PG) group of receptors. FP binds to and mediates the biological actions of prostaglandin F2α (PGF2α). It is encoded in humans by the PTGFR gene.
PGDS protein is a protein that in humans is encoded by the HPGDS gene.
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 D2 receptor 2 (DP2). The drug is being developed as a novel treatment for male pattern baldness by Allergan.
The prostaglandin D2 (PGD2) receptors are G protein-coupled receptors that bind and are activated by prostaglandin D2. Also known as PTGDR or DP receptors, they are important for various functions of the nervous system and inflammation. They include the following proteins:
The prostaglandin E2 (PGE2) receptors are G protein-coupled receptors that bind and are activated by prostaglandin E2. They are members of the prostaglandin receptors class of receptors and include the following Protein isoforms:
{{cite journal}}
: CS1 maint: numeric names: authors list (link){{cite journal}}
: CS1 maint: multiple names: authors list (link){{cite journal}}
: CS1 maint: multiple names: authors list (link){{cite journal}}
: CS1 maint: multiple names: authors list (link){{cite journal}}
: CS1 maint: multiple names: authors list (link){{cite journal}}
: CS1 maint: multiple names: authors list (link){{cite journal}}
: CS1 maint: multiple names: authors list (link)