Latanoprost

• CAT Number: A000003
• CAS Number: 130209-82-4
• Molecular Formula: C26H40O5
• Molecular Weight: 432.6
• Purity: ≥95%
• Synonyms: PHXA41; PHXA-41; PHXA 41; XA34; XA-34; XA 34; Latanoprost, Xalatan, Catioprost
• Target: Prostaglandin Receptor
• Solubility: 10 mM in DMSO
• Storage: -20°C
• IUPAC Name: propan-2-yl (Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(3R)-3-hydroxy-5-phenylpentyl]cyclopentyl]hept-5-enoate
• InChI: InChI=1S/C26H40O5/c1-19(2)31-26(30)13-9-4-3-8-12-22-23(25(29)18-24(22)28)17-16-21(27)15-14-20-10-6-5-7-11-20/h3,5-8,10-11,19,21-25,27-29H,4,9,12-18H2,1-2H3/b8-3-/t21-,22+,23+,24-,25+/m0/s1
• InChIKey: GGXICVAJURFBLW-CEYXHVGTSA-N
• SMILES: CC(C)OC(=O)CCCC=CCC1C(CC(C1CCC(CCC2=CC=CC=C2)O)O)O

Latanoprost (CAS 130209-82-4) is the isopropyl ester of 17-phenyl-13,14-dihydro prostaglandin F2α (17-phenyl-13,14-dihydro PGF2α). It is a prodrug form of the free acid, which is a potent agonist of the FP receptor in the eye. Latanoprost reduces intraocular pressure in glaucoma patients with few side effects. The EC50 value of latanoprost (tested as the free acid) for FP receptors is 3.6 nM.

Overview of Clinical Research

Latanoprost is a prostaglandin F2 alpha agonist developed by Kedalion Therapeutics.  Kedalion Therapeutics planed a phase II trial for Glaucoma in 2019.

Reference

1. Surv Ophthalmol. 1997 Feb;41 Suppl 2:S77-81.Clinical dose-regimen studies with latanoprost, a new ocular hypotensive PGF2 alpha analogue.Diestelhorst M(1), Krieglstein GK, Lusky M, Nagasubramanian S.

This review summarizes recent short-term clinical studies evaluating the ocular hypotensive efficacy of different dose-regimens of latanoprost. When tested in ocular hypertensive and glaucoma patients concomitantly treated with timolol, 0.006% latanoprost given only in the evening, was found to be more effective than the same concentration given in the morning and evening. In patients with open angle, pseudoexfoliation and normal tension glaucoma not receiving other treatment, once-daily 0.005% latanoprost monotherapy was more effective than twice-daily 0.0015% latanoprost treatment. No significant differences were found in conjunctival hyperemia, sensory irritation or blood-aqueous barrier permeability between these two treatment regimens. Although the ocular hypotensive efficacy of once-daily application of the lower concentration (0.0015%) latanoprost was not investigated, we would conclude, based on the studies reviewed here, that at a concentration of 0.005%, once-a-day dosing of latanoprost is highly effective in significantly reducing intraocular pressure, causing only minimal, clinically acceptable short-term ocular side effects.
2. Drugs Aging. 1996 Nov;9(5):363-78.Latanoprost. A review of its pharmacological properties, clinical efficacy and tolerability in the management of primary open-angle glaucoma and ocular hypertension.Patel SS(1), Spencer CM.

Latanoprost is an ester prodrug analogue of prostaglandin F2 alpha which effectively reduces intraocular pressure (IOP) by increasing uveoscleral outflow rather than altering conventional trabeculo-canalicular) aqueous outflow. The IOP-lowering effect of latanoprost lasts for 20 to 24 hours after a single dose, which allows a single daily dosage regimen. Data from 4 randomised double-masked multicentre studies indicate that a once daily dose of topical latanoprost 0.005% is as effective as timolol 0.5% twice daily in the treatment of patients with primary open-angle glaucoma or ocular hypertension. A number of studies also demonstrate that latanoprost enhances IOP-lowering effects when applied in combination with other antiglaucoma agents. Latanoprost is well tolerated with no, or barely detectable, conjunctival hyperaemia, and, unlike timolol, is not associated with systemic adverse effects. However, 3 to 10% of patients treated with latanoprost 0.005% have shown increased iris pigmentation after 3 to 4.5 months/' treatment. In summary, the available data show that latanoprost is a potent IOP-lowering agent with a number of positive features including a single daily dosage regimen, a novel mechanism of action that enhances the IOP-lowering effect of contemporary agents, and a lack of systemic adverse effects. These properties suitably poise latanoprost for a prominent position in the management of patients with primary open-angle glaucoma and ocular hypertension.
3. Curr Opin Ophthalmol. 1996 Apr;7(2):11-7.Latanoprost as a new horizon in the medical management of glaucoma.
Stjernschantz J(1), Alm A.

Latanoprost is a new prostaglandin F2 alpha analogue specifically developed for the treatment of glaucoma. Latanoprost is a selective FP receptor agonist, with a primary mode of action of increased uveoscleral outflow of aqueous humor. A dose of 50 micrograms/mL (0.005%) once daily has been found optimal in clinical trials. Latanoprost reduces the nocturnal intraocular pressure in addition to the diurnal, and has been shown to be additive to other glaucoma medication. In long-term phase III clinical trials, latanoprost 0.005% once daily has been proven to be at least as effective as timolol 0.5% twice a day. The main side effect of latanoprost is increased iridial pigmentation, which is relatively frequent in patients with mixed color of the iris. This unique side effect is based on the ability of prostaglandins to stimulate melanin formation in melanocytes. The advantages of latanoprost compared with other glaucoma medication comprise different mode of action, good intraocular pressure-reducing effect, once-daily dosing, and absence of systemic side effects. The long-term consequences of increased iridial pigmentation need to be further studied.