PGS-IN-1 (KME-4) is a potent inhibitor of prostaglandin synthetase (PGS, IC50: 0.28 μM) and 5-lipoxygenase (IC50: 1.05 μM).

8,11,14-Eicosatrienoic acid, also known as dihomo-γ-linolenic acid , is a polyunsaturated fatty acid (PUFA) produced from γ-linolenic acid by the action of fatty acid elongases. It can be metabolized by the cyclooxygenase pathway to produce 1-series prostaglandins (PGs) (e.g., PGE1). (±)14(15)-EpEDE is an EpEDE acid formed from 8,11,14-eicosatrienoic acid. This monoepoxide can be generated from the PUFA, in vitro, by the action of a strong oxidizing agent. Alternatively, this compound may be produced, in vivo, by epoxidation of the PUFA by cytochrome P450 epoxygenases. The biological properties of this compound are poorly understood.

The group IVA phospholipase A2 (PLA2), known as calcium-dependent cytosolic PLA2 (cPLA2), selectively releases arachidonic acid (AA) from membrane phospholipids, playing a central role in initiating the synthesis of prostaglandins (PGs) and leukotrienes (LTs). Pyrrophenone inhibits cPLA2α with an IC50 of 4.2 nM in enzyme assays and potently blocks the release of AA and the production of PGE2 and LTC4 in cells (IC50 = 24, 25, and 14 nM, respectively). Its action is reversible and selective, as pyrrophenone inhibits the secretory type IB and IIA PLA2s with more than a hundred-fold less potency. Pyrrophenone has also been shown to inhibit calcium ionophore (A23187)-stimulated AA release from monocytic cells, interleukin-1-induced PGE2 synthesis in mesangial cells, and the production of PGE2, LTs, and platelet-activating factor by human neutrophils, always with maximal inhibition at concentrations below 1 μM.

Prostaglandin E2 (PGE2) isopropyl ester is a more lipophilic form of the free acid, PGE2. PG esters have enhanced lipid solubility compared to their parent compounds. They are generally hydrolyzed to the free acid by endogenous esterases upon in vivo administration, making the esters useful prodrugs. In general, the C-1 esters of PGs show greatly diminished receptor activity in vitro compared to the parent free acids.

N-Desethyl Bimatoprost (17-phenyl trinor PGF2α amide) is an F-series PG analog in which the C-1 carboxyl group has been modified to an unsubstituted amide. PG esters have been shown to have ocular hypotensive activity. PG N-ethyl amides were recently introduced as alternative PG hypotensive prodrugs. Although it has been claimed that PG amides are not converted to the free acids in vivo, studies have shown that bovine and human corneal tissue converts the amides of various PGs to the free acids with a conversion efficiency of about 10-20% relative to the hydrolysis of isopropyl esters. 17-phenyl trinor PGF2α amide would be expected to show the typical intraocular effects of latanoprost, but with the much slower hydrolysis pharmacokinetics of the PG N-amides.

Bimatoprost is an F-series prostaglandin (PG) analog which has been approved for use as an ocular hypotensive drug. Oxidation of the C-15 hydroxyl group and amide hydrolysis of Bimatoprost produces 15-keto-17-phenyl trinor PGF2α. 15-keto-17-phenyl trinor PGF2α is a potential metabolite of bimatoprost when administered to animals. 15-keto PG analogs are potential minor impurities in commercial preparations of their corresponding bulk drug compounds. Although much less potent that the parent compound, 15-keto PGs still retain the ability to produce a small but measurable decrease (1 mm Hg) in the intraocular pressure of normal cynomolgus monkeys when administered at a dose of 1 μg/eye. 15-keto Latanoprost (15-keto-17-phenyl-13,14-dihydro trinor PGF2α isopropyl ester) is a miotic in the normal cat eye, causing an 8 mm reduction in pupillary diameter at 5 μg/eye. Again, this is not as potent as many other F-type PGs; for example, PGF2α will produce this degree of miosis at a dose of less than 1 μg/eye.

19(R)-Hydroxylated prostaglandins (PGs) are present at µg/ml concentrations in the semen of some mammalian species, notably primates, with the majority being from the PGE series and featuring a 15(S),19(R) hydroxyl stereochemistry. These compounds are also observed in marsupials' seminal plasma, where F-type 1 and 2-series compounds are predominant. The 15(R)-hydroxy epimer represents the inverse or unnatural isomer at C-15 for these 19-hydroxylated PGs. Although the biological function of 19(R)-hydroxylated PGs remains unclear, 19(R)-hydroxylation in the F-series leads to a notable reduction in receptor-mediated biological activity in certain assays.

There are currently four prostaglandin (PG) derivatives which have been approved for human clinical use for the treatment of glaucoma. The names of the PGs and the concentrations of the approved doses are: travoprost (40 μg/ml), latanoprost (50 μg/ml), bimatoprost (300 μg/ml), and unoprostone (1,500 μg/ml). All of these compounds are modified at C-1 in order to act as lipophilic prodrugs in the eye. All have also been postulated to function via activation of the prostanoid FP receptor. Unoprostone and bimatoprost stand out in this class due to their lack of potency. Both are also claimed to have alternate mechanisms of actions: as a docosanoid in the case of unoprostone and as a prostamide in the case of bimatoprost. Lumula is a hybrid eicosanoid analog which incorporates the docosanoid features of unoprostone as well as the prostamide features of bimatoprost. Based on classical structure-activity relationships which have been established for prostanoid receptors

Latanoprost is an F-series prostaglandin (PG) analog which has been approved for use as an ocular hypotensive drug. Oxidation of the C-15 hydroxyl group without isopropyl ester hydrolysis produces 15-keto latanoprost. 15-keto Latanoprost is a potential metabolite of latanoprost when administered to animals. 15-keto Latanoprost is also one of the common minor impurities found in commercial preparations of the bulk drug compound. Although much less potent that the parent compound latanoprost, 15-keto latanoprost still retains the ability to produce a small but measurable decrease (1 mm Hg) in the intraocular pressure of normal cynomolgus monkeys when administered at a dose of 1 μg/eye. 15-keto Latanoprost is also a miotic in the normal cat eye, causing an 8 mm reduction in pupillary diameter at 5 μg/eye. Again, this is not as potent as many other F-type PGs; for example, PGF2α will produce this degree of miosis at a dose of less than 1 μg/eye. Products of β-oxidation account for most of the metabolites of latanoprost recovered in plasma and urine. However, 15-keto latanoprost is a minor metabolite, and one which could be enhanced in situations where β-oxidation is reduced.