15-keto prostaglandin a-1

Prostaglandin A1 (PGA1) was first isolated as a dehydration product of the PGE1 compounds found in human semen. 15-keto PGA1 is a metabolite of PGA1, produced by 15-hydroxy PG dehydrogenase. It can be produced from PGA1 in pig lung, trachea, aorta, and pulmonary artery tissue preparations. 15-keto PGA1, given at a concentration of 6 μM, causes vasoconstriction of rabbit lung that is comparable to that induced by angiotensin II.

8-iso-15-keto Prostaglandin F2α (8-iso-15-keto PGF2α) is a metabolite of the isoprostane 8-iso PGF2α in rabbits, monkeys, and humans. 8-iso PGF2α is a prostaglandin-like product of non-specific lipid peroxidation. In humans and monkeys, exogenously infused 8-iso PGF2α is converted to metabolites with 2 or 4 carbon atoms removed from the top side chain by β-oxidation, with a similar pattern observed in tritiated 8-iso PGF2α-infused rabbits. Early in the infusion (within 1-2 minutes), 8-iso-15-keto PGF2α is a major component of the metabolite profile, primarily comprising unmetabolized 8-iso PGF2α. 8-iso-15-keto PGF2α is a vasoconstrictor when tested on the rat isolated thoracic aorta, acting via the TP (thromboxane) receptor.

Prostaglandin D1 (PGD1) is the theoretical D-series metabolite of dihomo-γ-linolenic acid (DGLA), but to date it has not been isolated as a natural product. It is an inhibitor of ADP-induced platelet aggregation in humans with an IC50 value of 320 ng/ml, about 1/10 as potent as PGD2. 13,14-dihydro-15-keto Prostaglandin D1 (13,14-dihydro-15-keto PGD1) is the theoretical metabolite of PGD1 via the 15-hydroxy PG dehydrogenase metabolic pathway. No biological studies for this compound have been reported.

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.

15-keto Latanoprost is a potential metabolite of latanoprost when administered to animals and is a common minor impurity in commercial preparations of the bulk drug compound. Although much less potent than latanoprost, 15-keto Latanoprost can still produce a small but measurable decrease (1 mm Hg) in intraocular pressure in normal cynomolgus monkeys at a dose of 1 μg/eye. It also acts as a miotic in normal cats, causing an 8 mm Hg reduction in pupillary diameter at 5 μg/eye, though it is not as potent as many other F-type prostaglandins, such as prostaglandin F2α, which achieves the same effect at less than 1 μg/eye.

Bimatoprost is an F-series prostaglandin (PG) analog 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, a potential metabolite when administered to animals. 15-keto PG analogs can be minor impurities in commercial preparations of corresponding bulk drug compounds. Although much less potent than the parent compound, 15-keto PGs can still produce a small but measurable decrease (1 mm Hg) in intraocular pressure of normal cynomolgus monkeys at a dose of 1 μg/eye. 15-keto Latanoprost (15-keto-17-phenyl-13,14-dihydro trinor PGF2α isopropyl ester) acts as a miotic in normal cat eyes, causing an 8 mm reduction in pupillary diameter at 5 μg/eye. This is less potent compared to many other F-type PGs; for example, PGF2α induces similar miosis at less than 1 μg/eye.

15-keto-Prostaglandin E2 is an endogenous bioactive metabolite that inhibits STAT3 activation through covalent interaction with the Cys259 residue, while also binding to and stabilizing EP2 and EP4 receptors, thereby exerting inhibitory effects on breast cancer cell growth and tumor progression, activating PPAR-γ signaling, and promoting fungal growth, collectively positioning this lipid mediator as a multifunctional regulator in cancer biology, immunometabolism, and host–pathogen interaction research.

13,14-Dihydro-15-keto prostaglandin D2 (DK-PGD2), a PGD2 metabolite formed by the 15-hydroxyl PGDH pathway, is a selective agonist for the DP2 receptor and can inhibit ion flux in canine colonic mucosa preparation [1].