ACS 67

An H2S-releasing latanoprost analog

Latanoprost is an F-series prostaglandin (PG) analog which has been approved for use as an ocular hypotensive drug for the treatment of glaucoma.1 Latanoprost is an isopropyl ester, a prodrug form which is converted to latanoprost (free acid) by endogenous esterase enzymes. The free acid form is 200 times more potent than latanoprost as an FP receptor ligand for the human recombinant FP receptor.2 ACS 67 is an analog of latanoprost (free acid) that contains a hydrogen sulfide releasing component conjugated to the latanoprost carboxyl group.3 In glaucomatous pigmented rabbits, ACS 67 reduced intra-ocular pressure (IOP) more rapidly and to a greater extent than latanoprost (15 versus 25.5 mm Hg at four hours) at a dose of 0.005% for each compound.3 ACS 67 also increased the levels of reduced glutathione and cGMP in the aqueous humor of glaucomatous pigmented rabbits better than latanoprost.3

598.8

≥95%

O[C@@H]1[C@H](C/C=C\CCCC(OC2=CC=C(C3=CC(SS3)=S)C=C2)=O)[C@@H](CC[C@@H](O)CCC4=CC=CC=C4)[C@H](O)C1

C32H38O5S3

1088434-86-9

≥ 4 years

DMF: 30 mg/ml DMSO: 20 mg/ml Ethanol: 2 mg/ml

1.Stjernschantz, J. and Resul, B. Phenyl substituted prostaglandin analogs for glaucoma treatment. Drugs of the Future 17, 691-704 (1992).
2.Abramovitz, M.,Adam, M.,Boie, Y., et al. The utilization of recombinant prostanoid receptors to determine the affinities and selectivities of prostaglandins and related analogs. Biochimica et Biophysica Acta 1483, 285-293 (2000).
3.Perrino, E.,Uliva, C.,Lanzi, C., et al. New prostaglandin derivative for glaucoma treatment. Bioorganic & Medicinal Chemistry Letters 19, 1639-1642 (2009).