WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H561500
CAS#: 860005-21-6
Description: Latanoprostene, also known as PF-3187207, is a a nitric oxide (NO)-donating latanoprost with prostaglandin activity. It loweres intraocular pressure (IOP) more effectively than latanoprost in monkeys, dogs and rabbits.
Hodoodo Cat#: H561500
Name: PF-3187207
CAS#: 860005-21-6
Chemical Formula: C27H41NO8
Exact Mass: 507.28
Molecular Weight: 507.620
Elemental Analysis: C, 63.89; H, 8.14; N, 2.76; O, 25.21
Synonym: PF-3187207; PF3187207; PF 3187207; Latanoprostene BUNOD; BOL-303259-X; NCX-116; NCX116; NCX116; Vesneo; Vyzulta;
IUPAC/Chemical Name: 4-Nitrooxybutyl (Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(3R)-3-hydroxy-5-phenylpentyl]cyclopentyl]hept-5-enoate
InChi Key: LOVMMUBRQUFEAH-UIEAZXIASA-N
InChi Code: InChI=1S/C27H41NO8/c29-22(15-14-21-10-4-3-5-11-21)16-17-24-23(25(30)20-26(24)31)12-6-1-2-7-13-27(32)35-18-8-9-19-36-28(33)34/h1,3-6,10-11,22-26,29-31H,2,7-9,12-20H2/b6-1-/t22-,23+,24+,25-,26+/m0/s1
SMILES Code: O=C(OCCCCO[N+]([O-])=O)CCC/C=C\C[C@@H]1[C@@H](CC[C@@H](O)CCC2=CC=CC=C2)[C@H](O)C[C@@H]1O
Appearance: Colorless to light yellow liquid
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
| Biological target: | Latanoprostene bunod (LBN), a nitric oxide (NO)-donating prostaglandin F2a analog, is a topical ophthalmic therapeutic for the reduction of intraocular pressure (IOP). |
| In vitro activity: | There was a significant increase in cGMP levels with 1, 3, 10, 30, and 100 μM LBN (Figs. 2A, 2C) and also with the NO donor SE 175 at both 10 and 100 μM (Figs. 2A, 2B). In contrast, there was no statistically significant effect of latanoprost on cGMP levels, except at 100 μM, when a small (approximately 60%) yet significant increase was observed (Fig. 2A). The EC50 for LBN for induction of HTMC cGMP levels was 1.5 ± 0.3 μM, and maximal efficacy was 320 ± 13%, whereas the EC50 for latanoprost could not be determined for the concentrations evaluated. To confirm the involvement of sGC in the elevation of cGMP levels by the two NO donors, the effect of the specific sGC inhibitor ODQ was determined. Incubation of HTMCs with ODQ (1 μM) prevented SE 175 and LBN induced cGMP generation (Figs. 2B, 2C). Reference: Invest Ophthalmol Vis Sci. 2015 Jun;56(6):4108-16. https://pubmed.ncbi.nlm.nih.gov/26114488/ |
| In vivo activity: | Rabbits are known to be sensitive to most IOP-lowering agents except for PGF2α agonists which makes this model ideal to dissect out NO-mediated effects for BOL-303259-X (PF3187207). The injection of 0.1 ml of hypertonic saline into the vitreous body led to a rapid (Tmax, 0.5 h) IOP rise from 16.9 ± 1.9 (baseline) to 45 ± 2.2 mmHg (Fig. 1) that decayed toward baseline over the following 5 h. BOL-303259-X (0.036%) significantly attenuated the saline-induced IOP rise throughout the experimental period (Fig. 1). The effects were maximal between 0.5 and 1.5 h with an average IOP difference versus vehicle of −13.5 ± 2.0 mmHg (−30%) (Fig. 1). As expected, an equimolar dose (0.030%) of latanoprost did not result in appreciable effects in this model. Reference: Exp Eye Res. 2011 Sep;93(3):250-5. https://pubmed.ncbi.nlm.nih.gov/21396362/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 30.0 | 59.10 |
The following data is based on the product molecular weight 507.62 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Cavet ME, Vollmer TR, Harrington KL, VanDerMeid K, Richardson ME. Regulation of Endothelin-1-Induced Trabecular Meshwork Cell Contractility by Latanoprostene Bunod. Invest Ophthalmol Vis Sci. 2015 Jun;56(6):4108-16. doi: 10.1167/iovs.14-16015. PMID: 26114488. 2. Krauss AH, Impagnatiello F, Toris CB, Gale DC, Prasanna G, Borghi V, Chiroli V, Chong WK, Carreiro ST, Ongini E. Ocular hypotensive activity of BOL-303259-X, a nitric oxide donating prostaglandin F2α agonist, in preclinical models. Exp Eye Res. 2011 Sep;93(3):250-5. doi: 10.1016/j.exer.2011.03.001. Epub 2011 Mar 9. PMID: 21396362. |
| In vitro protocol: | 1. Cavet ME, Vollmer TR, Harrington KL, VanDerMeid K, Richardson ME. Regulation of Endothelin-1-Induced Trabecular Meshwork Cell Contractility by Latanoprostene Bunod. Invest Ophthalmol Vis Sci. 2015 Jun;56(6):4108-16. doi: 10.1167/iovs.14-16015. PMID: 26114488. 2. Krauss AH, Impagnatiello F, Toris CB, Gale DC, Prasanna G, Borghi V, Chiroli V, Chong WK, Carreiro ST, Ongini E. Ocular hypotensive activity of BOL-303259-X, a nitric oxide donating prostaglandin F2α agonist, in preclinical models. Exp Eye Res. 2011 Sep;93(3):250-5. doi: 10.1016/j.exer.2011.03.001. Epub 2011 Mar 9. PMID: 21396362. |
| In vivo protocol: | 1. Krauss AH, Impagnatiello F, Toris CB, Gale DC, Prasanna G, Borghi V, Chiroli V, Chong WK, Carreiro ST, Ongini E. Ocular hypotensive activity of BOL-303259-X, a nitric oxide donating prostaglandin F2α agonist, in preclinical models. Exp Eye Res. 2011 Sep;93(3):250-5. doi: 10.1016/j.exer.2011.03.001. Epub 2011 Mar 9. PMID: 21396362. |
1: Pharmacoeconomic Review Report: Latanoprostene Bunod (Vyzulta): (Bausch Health, Canada Inc.): Indication: For the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2019 Aug. Available from http://www.ncbi.nlm.nih.gov/books/NBK549683/ PubMed PMID: 31742962.
2: Clinical Review Report: Latanoprostene Bunod (Vyzulta): (Bausch Health, Canada Inc.): Indication: For the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2019 Aug. Available from http://www.ncbi.nlm.nih.gov/books/NBK549676/ PubMed PMID: 31742961.
3: CADTH Canadian Drug Expert Committee Recommendation: Latanoprostene Bunod (Vyzulta — Bausch Health, Canada Inc.): Indication: For the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2019 Jul. No abstract available. Available from http://www.ncbi.nlm.nih.gov/books/NBK549613/ PubMed PMID: 31738493.
4: Mehran NA, Sinha S, Razeghinejad R. New glaucoma medications: latanoprostene bunod, netarsudil, and fixed combination netarsudil-latanoprost. Eye (Lond). 2019 Nov 6. doi: 10.1038/s41433-019-0671-0. [Epub ahead of print] Review. PubMed PMID: 31695162.
5: Fingeret M, Gaddie IB, Bloomenstein M. Latanoprostene bunod ophthalmic solution 0.024%: a new treatment option for open-angle glaucoma and ocular hypertension. Clin Exp Optom. 2019 Nov;102(6):541-550. doi: 10.1111/cxo.12853. Epub 2019 Jan 7. Review. PubMed PMID: 30614563.
6: Addis VM, Miller-Ellis E. Latanoprostene bunod ophthalmic solution 0.024% in the treatment of open-angle glaucoma: design, development, and place in therapy. Clin Ophthalmol. 2018 Dec 20;12:2649-2657. doi: 10.2147/OPTH.S156038. eCollection 2018. Review. PubMed PMID: 30587912; PubMed Central PMCID: PMC6304237.
7: Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006-. Available from http://www.ncbi.nlm.nih.gov/books/NBK500960/ PubMed PMID: 30000019.
8: Hoy SM. Correction to: Latanoprostene Bunod Ophthalmic Solution 0.024%: A Review in Open-Angle Glaucoma and Ocular Hypertension. Drugs. 2018 Jun;78(8):857. doi: 10.1007/s40265-018-0925-3. PubMed PMID: 29846910; PubMed Central PMCID: PMC5993835.
9: Hoy SM. Latanoprostene Bunod Ophthalmic Solution 0.024%: A Review in Open-Angle Glaucoma and Ocular Hypertension. Drugs. 2018 May;78(7):773-780. doi: 10.1007/s40265-018-0914-6. Review. Erratum in: Drugs. 2018 Jun;78(8):857. PubMed PMID: 29761382; PubMed Central PMCID: PMC5976683.
10: Weinreb RN, Liebmann JM, Martin KR, Kaufman PL, Vittitow JL. Latanoprostene Bunod 0.024% in Subjects With Open-angle Glaucoma or Ocular Hypertension: Pooled Phase 3 Study Findings. J Glaucoma. 2018 Jan;27(1):7-15. doi: 10.1097/IJG.0000000000000831. PubMed PMID: 29194198.
11: Cavet ME, DeCory HH. The Role of Nitric Oxide in the Intraocular Pressure Lowering Efficacy of Latanoprostene Bunod: Review of Nonclinical Studies. J Ocul Pharmacol Ther. 2018 Jan/Feb;34(1-2):52-60. doi: 10.1089/jop.2016.0188. Epub 2017 Aug 7. Review. PubMed PMID: 28783422; PubMed Central PMCID: PMC5963638.
12: Kaufman PL. Latanoprostene bunod ophthalmic solution 0.024% for IOP lowering in glaucoma and ocular hypertension. Expert Opin Pharmacother. 2017 Mar;18(4):433-444. doi: 10.1080/14656566.2017.1293654. Epub 2017 Feb 20. Review. PubMed PMID: 28234563.
13: Garcia GA, Ngai P, Mosaed S, Lin KY. Critical evaluation of latanoprostene bunod in the treatment of glaucoma. Clin Ophthalmol. 2016 Oct 18;10:2035-2050. eCollection 2016. Review. PubMed PMID: 27799730; PubMed Central PMCID: PMC5079698.
14: Kawase K, Vittitow JL, Weinreb RN, Araie M; JUPITER Study Group. Long-term Safety and Efficacy of Latanoprostene Bunod 0.024% in Japanese Subjects with Open-Angle Glaucoma or Ocular Hypertension: The JUPITER Study. Adv Ther. 2016 Sep;33(9):1612-27. doi: 10.1007/s12325-016-0385-7. Epub 2016 Jul 25. PubMed PMID: 27457469; PubMed Central PMCID: PMC5020123.
15: Liu JHK, Slight JR, Vittitow JL, Scassellati Sforzolini B, Weinreb RN. Efficacy of Latanoprostene Bunod 0.024% Compared With Timolol 0.5% in Lowering Intraocular Pressure Over 24 Hours. Am J Ophthalmol. 2016 Sep;169:249-257. doi: 10.1016/j.ajo.2016.04.019. Epub 2016 Jul 22. PubMed PMID: 27457257.
16: Medeiros FA, Martin KR, Peace J, Scassellati Sforzolini B, Vittitow JL, Weinreb RN. Comparison of Latanoprostene Bunod 0.024% and Timolol Maleate 0.5% in Open-Angle Glaucoma or Ocular Hypertension: The LUNAR Study. Am J Ophthalmol. 2016 Aug;168:250-259. doi: 10.1016/j.ajo.2016.05.012. Epub 2016 May 20. PubMed PMID: 27210275.
17: Weinreb RN, Scassellati Sforzolini B, Vittitow J, Liebmann J. Latanoprostene Bunod 0.024% versus Timolol Maleate 0.5% in Subjects with Open-Angle Glaucoma or Ocular Hypertension: The APOLLO Study. Ophthalmology. 2016 May;123(5):965-73. doi: 10.1016/j.ophtha.2016.01.019. Epub 2016 Feb 11. PubMed PMID: 26875002.
18: Araie M, Sforzolini BS, Vittitow J, Weinreb RN. Evaluation of the Effect of Latanoprostene Bunod Ophthalmic Solution, 0.024% in Lowering Intraocular Pressure over 24 h in Healthy Japanese Subjects. Adv Ther. 2015 Nov;32(11):1128-39. doi: 10.1007/s12325-015-0260-y. Epub 2015 Nov 12. PubMed PMID: 26563323; PubMed Central PMCID: PMC4662725.
19: Cavet ME, Vollmer TR, Harrington KL, VanDerMeid K, Richardson ME. Regulation of Endothelin-1-Induced Trabecular Meshwork Cell Contractility by Latanoprostene Bunod. Invest Ophthalmol Vis Sci. 2015 Jun;56(6):4108-16. doi: 10.1167/iovs.14-16015. PubMed PMID: 26114488.
20: Weinreb RN, Ong T, Scassellati Sforzolini B, Vittitow JL, Singh K, Kaufman PL; VOYAGER study group. A randomised, controlled comparison of latanoprostene bunod and latanoprost 0.005% in the treatment of ocular hypertension and open angle glaucoma: the VOYAGER study. Br J Ophthalmol. 2015 Jun;99(6):738-45. doi: 10.1136/bjophthalmol-2014-305908. Epub 2014 Dec 8. PubMed PMID: 25488946; PubMed Central PMCID: PMC4453588.
