Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C25H44O5 |
Molecular Weight | 424.6139 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 4 / 4 |
E/Z Centers | 1 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CCCCCCCC(=O)CC[C@H]1[C@H](O)C[C@H](O)[C@@H]1C\C=C/CCCC(=O)OC(C)C
InChI
InChIKey=XXUPXHKCPIKWLR-JHUOEJJVSA-N
InChI=1S/C25H44O5/c1-4-5-6-7-10-13-20(26)16-17-22-21(23(27)18-24(22)28)14-11-8-9-12-15-25(29)30-19(2)3/h8,11,19,21-24,27-28H,4-7,9-10,12-18H2,1-3H3/b11-8-/t21-,22-,23+,24-/m1/s1
DescriptionCurator's Comment: Description was created based on several sources, including
http://www.drugs.com/ppa/unoprostone.html
http://www.drugbank.ca/drugs/DB06826
http://www.rxlist.com/rescula-drug.htm
Curator's Comment: Description was created based on several sources, including
http://www.drugs.com/ppa/unoprostone.html
http://www.drugbank.ca/drugs/DB06826
http://www.rxlist.com/rescula-drug.htm
Unoprostone Isopropyl is a synthetic docosanoid and a structural analogue of an inactive biosynthetic cyclic derivative of arachidonic acid, 13,14-dihydro-15-keto-prostaglandin F 2a. Although the mechanism of action is unknown, unoprostone isopropyl is believed to reduce elevated intraocular pressure by increasing the outflow of aqueous humor through the trabecular meshwork. Unoprostone isopropyl (UI) may have a local effect on Big Potassium channels and ClC-2 chloride channels, but the exact mechanism is unknown at this time. Unoprostone is used for the management of open-angle glaucoma and ocular hypertension. The therapeutic efficacy of Unoprostone can be decreased when used in combination with Celecoxib, Diclofenac, Diflunisal, Etodolac and some other drugs. Unoprostone isopropyl ophthalmic solution may gradually increase the pigmentation of the iris, cause pigment changes (darkening) to periorbital pigmented tissues and eyelashes, exacerbate active intraocular inflammation (e.g., uveitis), and cause macular edema. In clinical studies, the most common ocular adverse reactions with use of Rescula were burning/stinging, burning/stinging upon drug instillation, dry eyes, itching, increased length of eyelashes, and injection. These were reported in approximately 10–25% of patients. Ocular adverse reactions occurring in approximately 5–10% of patients were abnormal vision, eyelid disorder, foreign body sensation, and lacrimation disorder. Other adverse reactions occurred more rarely.
Originator
Sources: http://uk.reuters.com/article/idUS221685+22-Mar-2011+BW20110322 | http://adisinsight.springer.com/drugs/800003136
Curator's Comment: R-Tech Ueno received the first marketing approval of unoprostone isopropyl in Japan in 1994 for the treatment of Glaucoma and Ocular Hypertension.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL1987 |
3280.0 nM [EC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | RESCULA Approved UseRescula (unoprostone isopropyl ophthalmic solution) 0.15% is indicated for the lowering of intraocular pressure in patients with open-angle glaucoma or ocular hypertension. Launch Date2000 |
|||
Primary | RESCULA Approved UseRescula (unoprostone isopropyl ophthalmic solution) 0.15% is indicated for the lowering of intraocular pressure in patients with open-angle glaucoma or ocular hypertension. Launch Date2000 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1.5 ng/mL |
1 drop 2 times / day multiple, ocular dose: 1 drop route of administration: Ocular experiment type: MULTIPLE co-administered: |
UNOPROSTONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
14 min |
1 drop 2 times / day multiple, ocular dose: 1 drop route of administration: Ocular experiment type: MULTIPLE co-administered: |
UNOPROSTONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
0.15 % 2 times / day steady, ophthalmic Recommended Dose: 0.15 %, 2 times / day Route: ophthalmic Route: steady Dose: 0.15 %, 2 times / day Sources: |
unhealthy, adult n = 659 Health Status: unhealthy Condition: glaucoma or ocular hypertension Age Group: adult Sex: unknown Population Size: 659 Sources: |
Disc. AE: Abnormal vision, Burning sensation... AEs leading to discontinuation/dose reduction: Abnormal vision (1.1%) Sources: Burning sensation (0.6%) Instillation site burning (0.3%) Conjunctivitis (0.5%) Sensation of foreign body (0.6%) Asthma (0.2%) Chest pain (0.2%) Insomnia (0.3%) Rash (0.5%) |
0.15 % 2 times / day steady, ophthalmic Recommended Dose: 0.15 %, 2 times / day Route: ophthalmic Route: steady Dose: 0.15 %, 2 times / day Sources: |
unhealthy, adult n = 77 Health Status: unhealthy Condition: intraocular pressure Age Group: adult Sex: unknown Population Size: 77 Sources: |
Disc. AE: Intraocular pressure increased... AEs leading to discontinuation/dose reduction: Intraocular pressure increased (2 patients) Sources: |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Asthma | 0.2% Disc. AE |
0.15 % 2 times / day steady, ophthalmic Recommended Dose: 0.15 %, 2 times / day Route: ophthalmic Route: steady Dose: 0.15 %, 2 times / day Sources: |
unhealthy, adult n = 659 Health Status: unhealthy Condition: glaucoma or ocular hypertension Age Group: adult Sex: unknown Population Size: 659 Sources: |
Chest pain | 0.2% Disc. AE |
0.15 % 2 times / day steady, ophthalmic Recommended Dose: 0.15 %, 2 times / day Route: ophthalmic Route: steady Dose: 0.15 %, 2 times / day Sources: |
unhealthy, adult n = 659 Health Status: unhealthy Condition: glaucoma or ocular hypertension Age Group: adult Sex: unknown Population Size: 659 Sources: |
Insomnia | 0.3% Disc. AE |
0.15 % 2 times / day steady, ophthalmic Recommended Dose: 0.15 %, 2 times / day Route: ophthalmic Route: steady Dose: 0.15 %, 2 times / day Sources: |
unhealthy, adult n = 659 Health Status: unhealthy Condition: glaucoma or ocular hypertension Age Group: adult Sex: unknown Population Size: 659 Sources: |
Instillation site burning | 0.3% Disc. AE |
0.15 % 2 times / day steady, ophthalmic Recommended Dose: 0.15 %, 2 times / day Route: ophthalmic Route: steady Dose: 0.15 %, 2 times / day Sources: |
unhealthy, adult n = 659 Health Status: unhealthy Condition: glaucoma or ocular hypertension Age Group: adult Sex: unknown Population Size: 659 Sources: |
Conjunctivitis | 0.5% Disc. AE |
0.15 % 2 times / day steady, ophthalmic Recommended Dose: 0.15 %, 2 times / day Route: ophthalmic Route: steady Dose: 0.15 %, 2 times / day Sources: |
unhealthy, adult n = 659 Health Status: unhealthy Condition: glaucoma or ocular hypertension Age Group: adult Sex: unknown Population Size: 659 Sources: |
Rash | 0.5% Disc. AE |
0.15 % 2 times / day steady, ophthalmic Recommended Dose: 0.15 %, 2 times / day Route: ophthalmic Route: steady Dose: 0.15 %, 2 times / day Sources: |
unhealthy, adult n = 659 Health Status: unhealthy Condition: glaucoma or ocular hypertension Age Group: adult Sex: unknown Population Size: 659 Sources: |
Burning sensation | 0.6% Disc. AE |
0.15 % 2 times / day steady, ophthalmic Recommended Dose: 0.15 %, 2 times / day Route: ophthalmic Route: steady Dose: 0.15 %, 2 times / day Sources: |
unhealthy, adult n = 659 Health Status: unhealthy Condition: glaucoma or ocular hypertension Age Group: adult Sex: unknown Population Size: 659 Sources: |
Sensation of foreign body | 0.6% Disc. AE |
0.15 % 2 times / day steady, ophthalmic Recommended Dose: 0.15 %, 2 times / day Route: ophthalmic Route: steady Dose: 0.15 %, 2 times / day Sources: |
unhealthy, adult n = 659 Health Status: unhealthy Condition: glaucoma or ocular hypertension Age Group: adult Sex: unknown Population Size: 659 Sources: |
Abnormal vision | 1.1% Disc. AE |
0.15 % 2 times / day steady, ophthalmic Recommended Dose: 0.15 %, 2 times / day Route: ophthalmic Route: steady Dose: 0.15 %, 2 times / day Sources: |
unhealthy, adult n = 659 Health Status: unhealthy Condition: glaucoma or ocular hypertension Age Group: adult Sex: unknown Population Size: 659 Sources: |
Intraocular pressure increased | 2 patients Disc. AE |
0.15 % 2 times / day steady, ophthalmic Recommended Dose: 0.15 %, 2 times / day Route: ophthalmic Route: steady Dose: 0.15 %, 2 times / day Sources: |
unhealthy, adult n = 77 Health Status: unhealthy Condition: intraocular pressure Age Group: adult Sex: unknown Population Size: 77 Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
yes [Km 93 uM] | ||||
yes | ||||
yes | ||||
Page: 6.0 |
yes |
PubMed
Title | Date | PubMed |
---|---|---|
Protective effects of sustained transscleral unoprostone delivery against retinal degeneration in S334ter rhodopsin mutant rats. | 2016 Nov |
|
Effect of topical isopropyl unoprostone on macular atrophy progression in eyes with exudative age-related macular degeneration. | 2017 Mar |
Patents
Sample Use Guides
Unoprostone isopropyl ophthalmic solution, 1.5 mg/mL. One drop in the affected eye(s) twice daily.
Route of Administration:
Topical
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26120274
Curator's Comment: The porcine retinal arterioles dilated in response to Unoprostone Isopropyl in a dose-dependent (100 pM-10 uM) manner. The highest concentration (10 uM) elicited about 30% of the maximal dilation.
The porcine retinal arterioles dilated in response to Unoprostone Isopropyl in a dose-dependent (100 pM-10 uM) manner. The highest concentration (10 uM) elicited about 30% of the maximal dilation.
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Classification Tree | Code System | Code | ||
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EU-Orphan Drug |
EU/3/13/1146
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NCI_THESAURUS |
C29705
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FDA ORPHAN DRUG |
314810
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NCI_THESAURUS |
C78568
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DTXSID5049071
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5282175
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31731
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m11304
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Unoprostone isopropyl
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120373-24-2
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C47778
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C072630
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135313
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DBSALT001760
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SUB15658MIG
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100000077315
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CHEMBL1200661
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5M161S5O5P
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ACTIVE MOIETY
METABOLITE INACTIVE (PARENT)
SUBSTANCE RECORD