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These are the most potent and efficacious medical therapies for lowering intraocular pressure (IOP), the most important risk factor identified for disease progression. They have few side effects and offer the convenience of once\u2010a\u2010day dosing. It was initially believed that endogenous PGs raised IOP and caused substantial ocular surface adverse effects. However, carefully designed experiments demonstrated that esterification of the carboxylic acid afforded potent and efficacious topical ocular hypotensive activity. The final hurdle to be overcome was improvement of the side effect profile. A hypothesis was advanced that the IOP\u2010lowering effect of PGF<jats:sub>2\u03b1<\/jats:sub>isopropyl ester was due to activation of its cognate PG\u2010FP receptor, while side effects were largely due to promiscuous interaction with other PG receptors. This hypothesis was validated by modification of the \u03c9 chain (carbons 13\u201320) to a phenyl group. This provided the first marketed FP\u2010class PG agonist analogue (FP\u2010PGA) ocular hypotensive agent, latanoprost. Since the introduction of latanoprost into clinical medicine to lower and control IOP, a number of additional FP\u2010PGAs have been discovered, characterized and marketed, including travoprost, tafluprost, unoprostone isopropyl ester and bimatoprost (an amide).<\/jats:p><\/jats:sec><jats:sec><jats:title>Linked Articles<\/jats:title><jats:p>This article is part of a themed section on Eicosanoids 35 years from the 1982 Nobel: where are we now? To view the other articles in this section visit<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v176.8\/issuetoc\">http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v176.8\/issuetoc<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14327","type":"journal-article","created":{"date-parts":[[2018,4,17]],"date-time":"2018-04-17T19:10:33Z","timestamp":1523992233000},"page":"1051-1058","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Discovery, characterization and clinical utility of prostaglandin agonists for the treatment of glaucoma"],"prefix":"10.1111","volume":"176","author":[{"given":"Peter G","family":"Klimko","sequence":"first","affiliation":[{"name":"Novartis Pharmaceuticals Corporation Fort Worth TX 76134 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4432-730X","authenticated-orcid":false,"given":"Najam A","family":"Sharif","sequence":"additional","affiliation":[{"name":"Santen Incorporated Emeryville CA 94608 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,5,17]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"Aerie Pharmaceuticals(2017).Aerie Pharmaceuticals Reports Positive Roclatan\u2122 (netarsudil\/latanoprost ophthalmic solution) 0.02%\/0.005% phase 3 12\u2010month topline safety results. 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