Identification
- Summary
Omidenepag isopropyl is an agonist of the prostaglandin EP2 receptor indicated for the reduction of elevated intraocular pressure.
- Brand Names
- Omlonti
- Generic Name
- Omidenepag isopropyl
- DrugBank Accession Number
- DB15071
- Background
Omidenepag isopropyl is a topical ocular hypotensive agent used to reduce intraocular pressure (IOP) in patients with glaucoma and ocular hypertension.6 Omidenepag isopropyl is quickly metabolized to its active metabolite, omidenepag, a molecule with high selectivity and agonistic activity towards the prostaglandin E2 (EP2) receptor.4,5 Prostanoid FP receptor agonists (FP agonists), such as latanoprost, are part of the first-line therapy for ocular hypertension and primary open-angle glaucoma; however, not all patients achieve adequate IOP reduction with FP agonists and require changes in treatment. The use of an EP2 receptor agonist such as omidenepag represents an alternative in these scenarios. Omidenepag IOP-lowering effect is comparable to the one observed with latanoprost.2 In 2018, omidenepag isopropyl was approved in Japan for the treatment of glaucoma and ocular hypertension.5 In September 2022, the FDA approved the use of omidenepag isopropyl.6
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Omidenepag isopropyl (DB15071)
- Weight
- Average: 520.61
Monoisotopic: 520.18927458 - Chemical Formula
- C26H28N6O4S
- Synonyms
- isopropyl N-(6-(((4-(1H-pyrazol-1-yl)benzyl)(3-pyridinylsulfonyl)amino)methyl)-2-pyridinyl)glycinate
- Omidenepag isopropyl
- External IDs
- DE-117
Pharmacology
- Indication
Omidenepag isopropyl ophthalmic solution (0.002%) is indicated for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension.6
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Glaucoma •••••••••••• •••••••• • ••••• Symptomatic treatment of Increased intra ocular pressure (iop) •••••••••••• •••••••• • ••••• Symptomatic treatment of Increased intra ocular pressure (iop) •••••••••••• •••••••• • ••••• - Contraindications & Blackbox Warnings
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Omidenepag isopropyl is rapidly hydrolyzed to its active metabolite, omidenepag. Omidenepag has a high affinity for the prostaglandin E2 (EP2) receptor and binds strongly with a Ki of 3.6 nM. Omidenepag also has high agonistic activity towards the EP2 receptor, with an EC50 of 8.3 nM, and has no effects over other receptors such as prostaglandin E1 (EP1) receptor and prostaglandin F receptor (FP). Unlike omidenepag, omidenepag isopropyl has weak or no affinity towards prostanoid receptors.4,5
The use of omidenepag isopropyl may lead to pigmentation of the iris, periorbital tissue and eyelash. The pigmentation of the iris is likely to be permanent, while the pigmentation of the periorbital tissue and eyelash are reversible in most patients. Patients receiving omidenepag isopropyl may also experience eyelash changes and ocular inflammation. Also, in patients with pseudophakia, the use of omidenepag isopropyl may lead to macular edema.6
- Mechanism of action
Omidenepag isopropyl is a prodrug of omidenepag, a relatively selective prostaglandin E2 (EP2) receptor agonist that decreases intraocular pressure (IOP). Elevated IOP is associated with glaucomatous field loss risk, and the higher the level of IOP, the greater the likelihood of optic nerve damage and visual field loss.6
The exact mechanism by which omidenepag lowers IOP is not fully elucidated; however, it has been suggested that by binding to the EP2 receptor, omidenepag causes an increase in aqueous humor outflow through the conventional and uveoscleral pathways.2,3 The EP2 receptor is present in different types of ocular tissues associated with aqueous humor dynamics, such as the ciliary muscle (CM) and trabecular meshwork (TM). The stimulation of EP2 receptors may lead to an increase in intracellular cyclic adenosine monophosphate (cAMP) and result in the relaxation of tissues in the CM and TM.3
Target Actions Organism AProstaglandin E2 receptor EP2 subtype agonistHumans UProstaglandin E2 receptor EP1 subtype agonistHumans - Absorption
The ophthalmic solution of omidenepag isopropyl is absorbed through the cornea, where it is hydrolyzed into its active metabolite, omidenepag. After the administration of one drop of omidenepag isopropyl 0.0025% eye drops to both eyes for 7 days, plasma concentration in humans reached Cmax at 10-15 minutes. There was no evidence of omidenepag isopropyl systemic accumulation, given that systemic exposure was similar between days 1 and 7.6 A study comparing the pharmacokinetic parameters of omidenepag in Japanese and Caucasian healthy subjects did not find significant differences. Japanese and Caucasian healthy subjects had a corresponding Cmax of 41.5 ± 20.1 and 27.2 ± 10.2 pg/mL, and a corresponding AUC0-8 h of 26.1 ± 5.7 and 15.3 ± 4.7 h·pg/mL (mean ± standard deviation).1
- Volume of distribution
Not available.
- Protein binding
The protein binding of omidenepag isopropyl is not available. The protein binding of its active metabolite, omidenepag, is 97.8%.7
- Metabolism
Omidenepag isopropyl is rapidly metabolized after topical ocular administration by carboxylesterase-1 to its pharmacologically active form, omidenepag. In the liver, omidenepag is further metabolized through oxidation, N-dealkylation, glucuronidation, sulfate conjugation or taurine conjugation.6 CYP3A4 plas an important role in the liver metabolism of omidenepag.1,7
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- Route of elimination
In rats given 0.03% omidenepag isopropyl in both eyes as a single dose (5 mcL/eye, 3 mcg/animal), 89% of the administered dose was excreted 168 hours after ocular instillation. Omidenepag was eliminated in feces (83%) and urine (4%).6
- Half-life
The half-life of omidenepag isopropyl is not available. The mean terminal half-life of its active metabolite, omidenepag, is approximately 30 minutes.7
- Clearance
Not available.
- Adverse Effects
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Toxicity information regarding omidenepag isopropyl is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as ocular inflammation.6 Symptomatic and supportive measures are recommended. Lifetime studies evaluating the carcinogenic effects of omidenepag isopropyl or omidenepag have not been performed. In rats given omidenepag isopropyl subcutaneously for 26 weeks, nephroblastoma and a spermatic cord tumor were developed at 0.003 mg/kg/day (33 times the recommended human ophthalmic dose). At 0.03 mg/kg/day (319 times the recommended human ophthalmic dose), rats given omidenepag isopropyl developed mammary adenocarcinoma and pituitary pars distalis adenomas. Based on the results of the in vitro mouse lymphoma forward mutation assay, omidenepag isopropyl (no metabolic activation) was mutagenic and clastogenic. Its active metabolite, omidenepag, was not mutagenic in the in vivo mouse micronucleus and bacterial reverse mutation tests.6
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Eybelis (Santen Pharmaceutical) / Omlonti (Santen Pharmaceutical)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Omlonti Solution / drops 0.02 mg/1mL Ophthalmic Santen Incorporated 2022-09-23 Not applicable US 
Categories
- ATC Codes
- G01AE10 — Combinations of sulfonamides
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- G0G0H52U6K
- CAS number
- 1187451-19-9
- InChI Key
- VIQCWEGEHRBLAC-UHFFFAOYSA-N
- InChI
- InChI=1S/C26H28N6O4S/c1-20(2)36-26(33)17-28-25-8-3-6-22(30-25)19-31(37(34,35)24-7-4-13-27-16-24)18-21-9-11-23(12-10-21)32-15-5-14-29-32/h3-16,20H,17-19H2,1-2H3,(H,28,30)
- IUPAC Name
- propan-2-yl 2-({6-[(N-{[4-(1H-pyrazol-1-yl)phenyl]methyl}pyridine-3-sulfonamido)methyl]pyridin-2-yl}amino)acetate
- SMILES
- CC(C)OC(=O)CNC1=CC=CC(CN(CC2=CC=C(C=C2)N2C=CC=N2)S(=O)(=O)C2=CC=CN=C2)=N1
References
- Synthesis Reference
Pharmaceutical composition for treating or preventing glaucoma (WO 2010/113957 A1). World Intellectual Property Organization. https://patents.google.com/patent/WO2010113957A1/en
- General References
- Aihara M, Lu F, Kawata H, Tanaka Y, Yamamura K, Odani-Kawabata N, Shams NK: Pharmacokinetics, Safety, and Intraocular Pressure-Lowering Profile of Omidenepag Isopropyl, a Selective, Nonprostaglandin, Prostanoid EP2 Receptor Agonist, in Healthy Japanese and Caucasian Volunteers (Phase I Study). J Ocul Pharmacol Ther. 2019 Dec;35(10):542-550. doi: 10.1089/jop.2019.0044. Epub 2019 Nov 1. [Article]
- Aihara M, Lu F, Kawata H, Iwata A, Odani-Kawabata N, Shams NK: Omidenepag Isopropyl Versus Latanoprost in Primary Open-Angle Glaucoma and Ocular Hypertension: The Phase 3 AYAME Study. Am J Ophthalmol. 2020 Dec;220:53-63. doi: 10.1016/j.ajo.2020.06.003. Epub 2020 Jun 10. [Article]
- Fuwa M, Toris CB, Fan S, Taniguchi T, Ichikawa M, Odani-Kawabata N, Iwamura R, Yoneda K, Matsugi T, Shams NK, Zhang JZ: Effects of a Novel Selective EP2 Receptor Agonist, Omidenepag Isopropyl, on Aqueous Humor Dynamics in Laser-Induced Ocular Hypertensive Monkeys. J Ocul Pharmacol Ther. 2018 Sep;34(7):531-537. doi: 10.1089/jop.2017.0146. Epub 2018 Jul 10. [Article]
- Kirihara T, Taniguchi T, Yamamura K, Iwamura R, Yoneda K, Odani-Kawabata N, Shimazaki A, Matsugi T, Shams N, Zhang JZ: Pharmacologic Characterization of Omidenepag Isopropyl, a Novel Selective EP2 Receptor Agonist, as an Ocular Hypotensive Agent. Invest Ophthalmol Vis Sci. 2018 Jan 1;59(1):145-153. doi: 10.1167/iovs.17-22745. [Article]
- Duggan S: Omidenepag Isopropyl Ophthalmic Solution 0.002%: First Global Approval. Drugs. 2018 Dec;78(18):1925-1929. doi: 10.1007/s40265-018-1016-1. [Article]
- FDA Approved Drug Products: OMLONTI (omidenepag isopropyl) ophthalmic solution 0.002%, for topical ophthalmic use [Link]
- FDA Thailand Product Information: EYBELIS (omidenepag isopropyl) ophthalmic solution 0.002% [Link]
- External Links
- ChemSpider
- 57643658
- BindingDB
- 50506549
- 2612690
- ChEMBL
- CHEMBL4297666
- Wikipedia
- Omidenepag
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Recruiting Treatment Normal Tension Glaucoma / Ocular Hypertension / Ocular Hypertension, Primary Open-angle Glaucoma (POAG) / Suspect Glaucoma 1 3 Completed Treatment Glaucoma and Ocular Hypertension 2 3 Completed Treatment Open Angle Glaucoma or Ocular Hypertension 2 3 Completed Treatment Primary Open Angle Glaucoma or Ocular Hypertension 1 3 Completed Treatment Primary Open-angle Glaucoma and Ocular Hypertension 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Solution / drops Ophthalmic 0.02 mg/1ml Solution Ophthalmic 0.02 mg/ml Solution / drops Ophthalmic 0.002 % - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US11197849 No 2021-12-14 2035-01-08 US US10702511 No 2020-07-07 2035-01-08 US US10179127 No 2019-01-15 2035-01-08 US US9415038 No 2016-08-16 2035-01-08 US USRE48183 No 2020-09-01 2035-01-08 US US10774072 No 2020-09-15 2035-06-10 US US8648097 No 2014-02-11 2029-10-13 US US8685986 No 2014-04-01 2029-10-13 US US10765750 No 2020-09-08 2035-01-08 US US11666563 No 2019-07-16 2039-07-16 US US11793798 No 2015-01-08 2035-01-08 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility Practically insoluble FDA label - Predicted Properties
Property Value Source Water Solubility 0.0162 mg/mL ALOGPS logP 3.08 ALOGPS logP 2.67 Chemaxon logS -4.5 ALOGPS pKa (Strongest Basic) 2.62 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 7 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 119.31 Å2 Chemaxon Rotatable Bond Count 11 Chemaxon Refractivity 141.29 m3·mol-1 Chemaxon Polarizability 53.42 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- Curator comments
- The hydrolyzed form of omidenepag isopropyl (omidenepag) binds to the EP2 receptor.
- General Function
- Prostaglandin e receptor activity
- Specific Function
- Receptor for prostaglandin E2 (PGE2). The activity of this receptor is mediated by G(s) proteins that stimulate adenylate cyclase. The subsequent raise in intracellular cAMP is responsible for the ...
- Gene Name
- PTGER2
- Uniprot ID
- P43116
- Uniprot Name
- Prostaglandin E2 receptor EP2 subtype
- Molecular Weight
- 39759.945 Da
References
- Kirihara T, Taniguchi T, Yamamura K, Iwamura R, Yoneda K, Odani-Kawabata N, Shimazaki A, Matsugi T, Shams N, Zhang JZ: Pharmacologic Characterization of Omidenepag Isopropyl, a Novel Selective EP2 Receptor Agonist, as an Ocular Hypotensive Agent. Invest Ophthalmol Vis Sci. 2018 Jan 1;59(1):145-153. doi: 10.1167/iovs.17-22745. [Article]
- FDA Approved Drug Products: OMLONTI (omidenepag isopropyl) ophthalmic solution 0.002%, for topical ophthalmic use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- Curator comments
- Omidenepag isopropyl is a weak agonist of EP1.
- General Function
- Prostaglandin e receptor activity
- Specific Function
- Receptor for prostaglandin E2 (PGE2). The activity of this receptor is mediated by G(q) proteins which activate a phosphatidylinositol-calcium second messenger system. May play a role as an importa...
- Gene Name
- PTGER1
- Uniprot ID
- P34995
- Uniprot Name
- Prostaglandin E2 receptor EP1 subtype
- Molecular Weight
- 41800.655 Da
References
- Kirihara T, Taniguchi T, Yamamura K, Iwamura R, Yoneda K, Odani-Kawabata N, Shimazaki A, Matsugi T, Shams N, Zhang JZ: Pharmacologic Characterization of Omidenepag Isopropyl, a Novel Selective EP2 Receptor Agonist, as an Ocular Hypotensive Agent. Invest Ophthalmol Vis Sci. 2018 Jan 1;59(1):145-153. doi: 10.1167/iovs.17-22745. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Carboxylic ester hydrolase activity
- Specific Function
- Not Available
- Gene Name
- CES1A1a
- Uniprot ID
- Q6LAP9
- Uniprot Name
- Carboxylesterase
- Molecular Weight
- 1908.25 Da
References
- FDA Approved Drug Products: OMLONTI (omidenepag isopropyl) ophthalmic solution 0.002%, for topical ophthalmic use [Link]
Drug created at May 20, 2019 14:47 / Updated at December 01, 2022 11:29