Omidenepag isopropyl
(Synonyms: DE-117) 目录号 : GC61157
Omidenepagisopropyl是选择性的，非前列腺素的EP2受体激动剂。Omidenepagisopropyl在角膜穿透过程中转化为活性产品Omidenepag，Omidenepag是高度选择性的EP2受体激动剂。Omidenepagisopropyl对EP1，EP2和FP受体有弱亲和力。Omidenepagisopropyl可以降低眼内压(IOP)，有潜力用于青光眼的研究。
Cas No.:1187451-19-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Omidenepag isopropyl is a selective EP2 receptor agonist. Omidenepag isopropyl is converted to the active product Omidenepag during corneal penetration, and Omidenepag is a highly selective EP2 receptor agonist. Omidenepag isopropyl shows only weak affinity for EP1, EP2, and FP receptors. Omidenepag isopropyl is under development for the treatment of glaucoma as an intraocular pressure (IOP)-lowering drug[1][2].
Omidenepag isopropyl at 0.0001%, 0.001%, or 0.01%, Xalatan, or vehicle was topically administered to one eye in ocular normotensive monkeys. IOP change after drug administration was compared to the predosing baseline value established on day 1. Omidenepag isopropyl also shows significant and dose-dependent IOP-lowering effects at doses of 0.0001%, 0.001%, and 0.01% in ocular normotensive monkeys, with mean maximal IOP reductions of 2.4 ± 0.6, 7.6 ± 1.7, and 13.3 ± 1.2 mm Hg at each tested concentration, respectively. The significant decreases in IOP for 0.001% and 0.01% OMDI at time 0 of day 7. Omidenepag isopropyl is hydrolyzed in the eye to Omidenepag (OMD), an EP2 receptor agonist , with a significant ocular hypotensive effect in both ocular normotensive and hypertensive animal models[1].In ocular hypertensive monkeys finds that Omidenepag isopropyl lowers IOP by increasing both trabecular outflow facility and uveoscleral outflow[2].
[1]. Kirihara T, et al. 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. [2]. Fuwa M, et al. 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.
| Cas No. | 1187451-19-9 | SDF | |
| 别名 | DE-117 | ||
| Canonical SMILES | O=C(OC(C)C)CNC1=NC(CN(CC2=CC=C(N3N=CC=C3)C=C2)S(=O)(C4=CC=CN=C4)=O)=CC=C1 | ||
| 分子式 | C26H28N6O4S | 分子量 | 520.6 |
| 溶解度 | DMSO : 50 mg/mL (96.04 mM; Need ultrasonic) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9209 mL | 9.6043 mL | 19.2086 mL |
| 5 mM | 0.3842 mL | 1.9209 mL | 3.8417 mL |
| 10 mM | 0.1921 mL | 0.9604 mL | 1.9209 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
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.PMID:32533949DOI:10.1016/j.ajo.2020.06.003.
Purpose: To evaluate the efficacy and safety of Omidenepag isopropyl (OMDI), a selective, non-prostaglandin, prostanoid EP2 receptor agonist, in Japanese patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT). Design: Phase III, randomized, investigator-masked, active-controlled, parallel-group, noninferiority study (ClinicalTrials.govNCT02623738). Methods: After a washout period of 1-4 weeks, eligible patients were randomized (1:1) to OMDI 0.002% or latanoprost 0.005% once daily for 4 weeks. Intraocular pressure (IOP) was measured at 9:00 AM, 1:00 PM, and 5:00 PM at weeks 1, 2, and 4. The primary endpoint was the change from baseline in mean diurnal IOP at week 4. The noninferiority margin for OMDI versus latanoprost was 1.5 mm Hg. Adverse events (AEs) were recorded. Results: Of the 190 patients randomized, 189 had at least 1 post-baseline IOP measurement. At baseline, patients who received OMDI or latanoprost had a mean ± SD diurnal IOP of 23.78 ± 1.73 mm Hg and 23.40 ± 1.51 mm Hg, respectively. At week 4, least-squares mean ± SE reduction in IOP from baseline with OMDI (-5.93 ± 0.23 mm Hg) was noninferior to that of latanoprost (-6.56 ± 0.22 mm Hg; 95% confidence interval between groups: 0.01-1.26). The most frequently reported treatment-related ocular AEs (OMDI vs latanoprost) were conjunctival hyperemia (23/94 patients [24.5%] vs 10/96 patients [10.4%]), corneal thickening (11/94 patients [11.7%] vs 1/96 patients [1.0%]), and punctate keratitis (0/94 patients vs 5/96 patients [5.2%]). No serious AEs were observed in either group, and there were no discontinuations related to the study drug. Conclusions: OMDI 0.002% was noninferior to latanoprost 0.005% in reducing IOP in patients with OHT or POAG and was well tolerated.
Omidenepag isopropyl for the treatment of glaucoma and ocular hypertension
Drugs Today (Barc) 2019 Jun;55(6):377-384.PMID:31250842DOI:10.1358/dot.2019.55.6.2984806.
Glaucoma is a main cause of irreversible vision impairment and its prevalence is expected to rise significantly in the near future. Among the current medications, prostaglandin analogues (PGAs) are widely used and considered as a first-line strategy in the management of glaucoma and ocular hypertension (OHT). However, given the non-negligible incidence of adverse ocular effects (conjunctival hyperemia, increase of iris pigmentation and eyelash changes) due to the use of this class of drugs, novel PGAs are being investigated. Omidenepag isopropyl is a selective prostaglandin EP2 receptor agonist which was approved on September 21, 2018, in Japan for the treatment of glaucoma and OHT. In this review, we will discuss its pharmacokinetics, pharmacodynamics and clinical efficacy, focusing also on its safety and tolerability profile.
Omidenepag isopropyl Ophthalmic Solution 0.002%: First Global Approval
Drugs 2018 Dec;78(18):1925-1929.PMID:30465134DOI:10.1007/s40265-018-1016-1.
Omidenepag isopropyl ophthalmic solution 0.002% (EYBELIS®) is a selective prostaglandin E2 receptor 2 agonist with a non-prostaglandin structure that is being developed by Ube Industries and Santen Pharmaceutical in Japan, Singapore and the USA for the treatment of glaucoma and ocular hypertension. Based on results from phase III trials, Omidenepag isopropyl ophthalmic solution 0.002% received approval in Japan in September 2018 for this indication. This article summarizes the milestones in the development of Omidenepag isopropyl ophthalmic solution 0.002% leading to this first global approval for the treatment of glaucoma and ocular hypertension.
Efficacy and Patient Tolerability of Omidenepag isopropyl in the Treatment of Glaucoma and Ocular Hypertension
Clin Ophthalmol 2022 Apr 26;16:1261-1279.PMID:35510270DOI:10.2147/OPTH.S340386.
Current therapeutic approaches for glaucoma aim to reduce intraocular pressure (IOP), which is the only available and reliable strategy proven to control the risk of disease development and progression. Omidenepag isopropyl (OMDI) is a novel topical ocular hypotensive agent that was launched onto the market for the treatment of glaucoma and ocular hypertension (OHT). After topical instillation and during corneal penetration, OMDI is converted into the active metabolite omidenepag (OMD), which behaves as a non-prostaglandin, selective E-prostanoid subtype 2 (EP2) receptor agonist. The topical administration of 0.002% OMDI once-daily (QD) possesses a 20-35% IOP-lowering effect, comparable to that of prostaglandin analogs targeting F-prostanoid (FP) receptor QD, which are the current first-line for pharmaceutical reduction of IOP. However, the mechanism of action and adverse events (AEs) of OMDI are different from those of FP receptor agonists. OMDI reduces IOP by enhancing both conventional trabecular and uveoscleral outflow facilities without complications of prostaglandin-associated periorbitopathy (PAP) seen with FP receptor agonists. Moreover, OMDI was also effective and well-tolerated in non-/poor responders to latanoprost and showed a stable IOP-lowering effect for one year, and its concomitant use with timolol enhanced the IOP-lowering effect. OMDI demonstrated acceptable safety and tolerability with good adherence and can be used in almost every patient. However, OMDI has some AEs such as conjunctival hyperemia, corneal thickening, macular edema/cystoid macular edema and ocular inflammation. Moreover, OMDI is contraindicated in patients who are allergic to the product, in aphakic or pseudophakic eyes, and in combination with tafluprost eye drops. If used appropriately in the right patients, OMDI could be an effective treatment option for glaucoma and OHT as a first-line alternative to FP agonists. Here, we summarize the results of clinical studies of OMDI and discuss its efficacy and patient tolerability in glaucoma and OHT in this review.
Periocular Adverse Reactions to Omidenepag isopropyl
Am J Ophthalmol 2022 May;237:114-121.PMID:34942112DOI:10.1016/j.ajo.2021.12.011.
Purpose: To investigate the periocular adverse reactions to Omidenepag isopropyl (OMDI). Design: Nonrandomized comparative clinical study. Methods: We enrolled 100 patients (100 eyes) with primary open-angle glaucoma or ocular hypertension who received initial treatment with OMDI or tafluprost in only 1 eye for ≥6 months. Photographs of the eyelids were taken on the day of the participants' visit after ≥6 months of prescription. Subsequently, 3 ophthalmologists individually determined the occurrence of eyelid pigmentation, eyelash growth, and deepening of the upper eyelid sulcus (DUES). Additionally, a questionnaire on the subjective symptoms was administered. Multivariate analysis of baseline data was performed to investigate the factors involved in adverse reactions. Results: The mean duration of drug administration was 10.2 ± 3.8 and 10.8 ± 4.1 months in the OMDI and tafluprost groups, respectively. The frequencies of eyelid pigmentation, eyelash growth, and DUES were 0.0%, 0.0%, and 2.0%, respectively, in the OMDI group, whereas the corresponding values in the tafluprost group were 4.0%, 32.0%, and 12.0%. The only significant difference was that the OMDI group showed fewer patients with eyelash growth than in the tafluprost group (P < .0001). In the questionnaire, the subjective symptoms of eyelid pigmentation, eyelash growth, and DUES were 8.0%, 2.0%, and 4.0%, respectively, in the OMDI group, whereas the corresponding values in the tafluprost group were 12.0%, 40.0%, and 4.0%, respectively. Multivariate analysis revealed a correlation between the type of drug administered and these adverse reactions (R = 0.38, P = .005). Conclusions: The frequencies of periocular adverse reactions to OMDI, ranging from 0% to 2.0%, were lower than those to tafluprost.