Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C27H41NO8 |
Molecular Weight | 507.6163 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 5 / 5 |
E/Z Centers | 1 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
O[C@H](CC[C@H]1[C@H](O)C[C@H](O)[C@@H]1C\C=C/CCCC(=O)OCCCCO[N+]([O-])=O)CCC2=CC=CC=C2
InChI
InChIKey=LOVMMUBRQUFEAH-UIEAZXIASA-N
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
Molecular Formula | C27H41NO8 |
Molecular Weight | 507.6163 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 5 / 5 |
E/Z Centers | 1 |
Optical Activity | UNSPECIFIED |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/9698288 | https://www.ncbi.nlm.nih.gov/pubmed/21788077http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020597s045s048lbl.pdfhttps://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207795Orig1s000lbl.pdfCurator's Comment: The description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/29194198 | https://clinicaltrials.gov/ct2/show/NCT01895972 | https://www.ncbi.nlm.nih.gov/pubmed/28783422 | https://clinicaltrials.gov/ct2/show/NCT01749904
Sources: https://www.ncbi.nlm.nih.gov/pubmed/9698288 | https://www.ncbi.nlm.nih.gov/pubmed/21788077http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020597s045s048lbl.pdfhttps://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207795Orig1s000lbl.pdf
Curator's Comment: The description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/29194198 | https://clinicaltrials.gov/ct2/show/NCT01895972 | https://www.ncbi.nlm.nih.gov/pubmed/28783422 | https://clinicaltrials.gov/ct2/show/NCT01749904
Latanoprostene Bunod (LBN) is a topical ophthalmic therapeutic for the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. There is no cure for glaucoma and therapeutic management is predominantly focused on minimizing disease progression and clinical sequelae via the reduction and maintenance of appropriate target IOPs. Latanoprostene Bunod is thought to lower intraocular pressure via a dual mechanism of action since the medication is metabolized into two relevant moieties upon administration: latanoprost acid, and butanediol mononitrate. As a prostaglandin F2-alpha analog, the latanoprost acid moiety operates as a selective PGF2-alpha (FP) receptor agonist. Since FP receptors occur in the ciliary muscle, ciliary epithelium, and sclera the latanoprost acid moiety primarily acts in the uveoscleral pathway where it increases the expression of matrix metalloproteinases (MMPs) like MMP-1, -3, and -9 which promote the degradation of collagen types I, III, and IV in the longitudinal bundles of the ciliary muscle and surrounding sclera. The resultant extracellular matrix remodeling of the ciliary muscle consequently produces reduced outflow resistance via increased permeability and increased aqueous humor outflow through the uveoscleral route. Conversely, the butanediol mononitrate undergoes further metabolism to NO and an inactive 1,4-butanediol moiety. As a gas that can freely diffuse across plasma membranes, it is proposed that the relaxing effect of NO to induce reductions in the cell volume and contractility of vascular smooth muscle-like cells is dependent upon activation of the sGC/cGMP/PKG cascade pathway. NO released from butanediol mononitrate consequently enters the cells of the TM and an inner wall of SC, causing decreases in myosin light chain-2 phosphorylation, increased phosphorylation of large-conductance calcium-activated potassium (BKCa) channels, and a subsequent efflux of potassium ions through such BKCa channels. All of these changes serve to decrease the cell contractility and volume, as well as to rearrange the actin cytoskeleton of the TM and SC cells. These biomechanical changes ultimately allow for enhanced conventional outflow of aqueous humor.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: P43088 Gene ID: 5737.0 Gene Symbol: PTGFR Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/10634944 |
3.6 nM [EC50] | ||
Target ID: CHEMBL1987 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9733584 |
|||
Target ID: CHEMBL1987 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | VYZULTA Approved UseVYZULTA is a prostaglandin analog indicated for the reduction of intraocular pressure in patients with open-angle glaucoma or ocular hypertension Launch Date1.48668482E12 |
|||
Primary | VYZULTA Approved UseVYZULTA is a prostaglandin analog indicated for the reduction of intraocular pressure in patients with open-angle glaucoma or ocular hypertension Launch Date1.48668482E12 |
|||
Primary | VYZULTA Approved UseYZULTA™ (latanoprostene bunod ophthalmic solution) 0.024% is indicated for the reduction of intraocular
pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. Launch Date1.50949436E12 |
|||
Primary | VYZULTA Approved UseYZULTA™ (latanoprostene bunod ophthalmic solution) 0.024% is indicated for the reduction of intraocular
pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. Launch Date1.50949436E12 |
|||
Palliative | XALATAN Approved UseXALATAN Sterile Ophthalmic Solution is indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. Launch Date8.3393282E11 |
|||
Primary | XALATAN Approved UseXALATAN Sterile Ophthalmic Solution is indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. Launch Date8.3393282E11 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
53 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12204697/ |
1.5 μg single, ocular dose: 1.5 μg route of administration: Ocular experiment type: SINGLE co-administered: |
LATANOPROST ACID plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
7.15 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12204697/ |
3 μg/kg bw single, intravenous dose: 3 μg/kg bw route of administration: Intravenous experiment type: SINGLE co-administered: |
LATANOPROST ACID plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
34 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12204697/ |
1.5 μg single, ocular dose: 1.5 μg route of administration: Ocular experiment type: SINGLE co-administered: |
LATANOPROST ACID plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
16.6 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12204697/ |
3 μg/kg bw single, intravenous dose: 3 μg/kg bw route of administration: Intravenous experiment type: SINGLE co-administered: |
LATANOPROST ACID plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
17 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12204697/ |
1.5 μg single, ocular dose: 1.5 μg route of administration: Ocular experiment type: SINGLE co-administered: |
LATANOPROST ACID plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
0.005 % 1 times / day multiple, topical Recommended Dose: 0.005 %, 1 times / day Route: topical Route: multiple Dose: 0.005 %, 1 times / day Sources: |
unhealthy, mean age 63.1 years n = 289 Health Status: unhealthy Condition: open-angle glaucoma | ocular hypertension Age Group: mean age 63.1 years Sex: M+F Population Size: 289 Sources: |
Disc. AE: Iritis, Meibomianitis... AEs leading to discontinuation/dose reduction: Iritis (grade 2, 0.3%) Sources: Meibomianitis (grade 1, 0.3%) |
11 ug/kg multiple, topical MTD Dose: 11 ug/kg Route: topical Route: multiple Dose: 11 ug/kg Sources: |
unhealthy Health Status: unhealthy Sources: |
|
10 ug/kg single, intravenous (max) Overdose Dose: 10 ug/kg Route: intravenous Route: single Dose: 10 ug/kg Sources: |
healthy Health Status: healthy Sources: |
Other AEs: Abdominal pain, Dizziness... Other AEs: Abdominal pain Sources: Dizziness Fatigue Hot flushes Nausea Sweating |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Meibomianitis | grade 1, 0.3% Disc. AE |
0.005 % 1 times / day multiple, topical Recommended Dose: 0.005 %, 1 times / day Route: topical Route: multiple Dose: 0.005 %, 1 times / day Sources: |
unhealthy, mean age 63.1 years n = 289 Health Status: unhealthy Condition: open-angle glaucoma | ocular hypertension Age Group: mean age 63.1 years Sex: M+F Population Size: 289 Sources: |
Iritis | grade 2, 0.3% Disc. AE |
0.005 % 1 times / day multiple, topical Recommended Dose: 0.005 %, 1 times / day Route: topical Route: multiple Dose: 0.005 %, 1 times / day Sources: |
unhealthy, mean age 63.1 years n = 289 Health Status: unhealthy Condition: open-angle glaucoma | ocular hypertension Age Group: mean age 63.1 years Sex: M+F Population Size: 289 Sources: |
Abdominal pain | 10 ug/kg single, intravenous (max) Overdose Dose: 10 ug/kg Route: intravenous Route: single Dose: 10 ug/kg Sources: |
healthy Health Status: healthy Sources: |
|
Dizziness | 10 ug/kg single, intravenous (max) Overdose Dose: 10 ug/kg Route: intravenous Route: single Dose: 10 ug/kg Sources: |
healthy Health Status: healthy Sources: |
|
Fatigue | 10 ug/kg single, intravenous (max) Overdose Dose: 10 ug/kg Route: intravenous Route: single Dose: 10 ug/kg Sources: |
healthy Health Status: healthy Sources: |
|
Hot flushes | 10 ug/kg single, intravenous (max) Overdose Dose: 10 ug/kg Route: intravenous Route: single Dose: 10 ug/kg Sources: |
healthy Health Status: healthy Sources: |
|
Nausea | 10 ug/kg single, intravenous (max) Overdose Dose: 10 ug/kg Route: intravenous Route: single Dose: 10 ug/kg Sources: |
healthy Health Status: healthy Sources: |
|
Sweating | 10 ug/kg single, intravenous (max) Overdose Dose: 10 ug/kg Route: intravenous Route: single Dose: 10 ug/kg Sources: |
healthy Health Status: healthy Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/020597Orig1s000rev.pdf#page=342 Page: 342.0 |
unlikely | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/020597Orig1s000rev.pdf#page=342 Page: 342.0 |
unlikely |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | ||||
no | ||||
unlikely | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/20019365/ Page: 6.0 |
weak | |||
yes | ||||
yes | ||||
yes |
PubMed
Title | Date | PubMed |
---|---|---|
Corneal permeability to and ocular metabolism of phenyl substituted prostaglandin esters in vitro. | 1994 Apr |
|
A comparison of latanoprost and timolol in primary open-angle glaucoma and ocular hypertension. A 12-week study. | 1996 Aug |
|
Mechanism of prostaglandin E2-, F2alpha- and latanoprost acid-induced relaxation of submental veins. | 1997 Dec 11 |
|
The lack of respiratory effects of the ocular hypotensive drug latanoprost in patients with moderate-steroid treated asthma. | 1997 Feb |
|
The utilization of recombinant prostanoid receptors to determine the affinities and selectivities of prostaglandins and related analogs. | 2000 Jan 17 |
|
A randomized, comparative open-label study on the efficacy of latanoprost and timolol in steroid induced ocular hypertension after photorefractive keratectomy. | 2000 Jul-Sep |
|
[Increased iris pigmentation after use of latanoprost in Japanese brown eyes]. | 2001 May |
|
Latanoprost and brimonidine: therapeutic and physiologic assessment before and after oral nonsteroidal anti-inflammatory therapy. | 2002 Jan |
|
Syncope and falls due to timolol eye drops. | 2006 Apr 22 |
|
Prospective comparative switch study from timolol 0.5% and latanoprost 0.005% to bimatoprost 0.03%. | 2006 Jan-Feb |
|
Comparison of the effects of bimatoprost and a fixed combination of latanoprost and timolol on circadian intraocular pressure. | 2007 Dec |
|
Latanoprost-related transient incontinence. | 2007 May-Jun |
|
Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. | 2015 May 18 |
Sample Use Guides
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/9537815
The mechanism of prostaglandin E2-, prostaglandin F2alpha- and latanoprost acid-induced relaxation of the rabbit submental vein was studied. Both prostaglandin F2alpha and the relatively selective FP receptor agonist, latanoprost acid, caused relaxation of the veins to about 50% of the precontracted state in the presence of GR 32191B, a thromboxane receptor antagonist (EC50: for prostaglandin F2alpha 7.9 x 10(-9) M, and for latanoprost acid 4.9 x 10(-9) M).
Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 17 16:19:41 UTC 2022
by
admin
on
Sat Dec 17 16:19:41 UTC 2022
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Record UNII |
I6393O0922
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Record Status |
Validated (UNII)
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Record Version |
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Latanoprostene bunod
Created by
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5261
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I6393O0922
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DB11660
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1988390
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Latanoprostene Bunod
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I6393O0922
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11156438
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9629
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860005-21-6
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CHEMBL2364612
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ZZ-133
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C170095
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M12042
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DTXSID101027765
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Related Record | Type | Details | ||
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METABOLITE -> PARENT | |||
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METABOLITE -> PARENT | |||
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METABOLITE INACTIVE -> PARENT | |||
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METABOLITE -> PARENT | |||
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METABOLITE -> PARENT | |||
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METABOLITE ACTIVE -> PRODRUG |
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METABOLITE -> PARENT | |||
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METABOLITE -> PARENT | |||
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METABOLITE ACTIVE -> PRODRUG |
Related Record | Type | Details | ||
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ACTIVE MOIETY |