U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C27H41NO8
Molecular Weight 507.6174
Optical Activity UNSPECIFIED
Defined Stereocenters 5 / 5
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of LATANOPROSTENE BUNOD

SMILES

C(\[H])(=C(\[H])/C[C@]1([H])[C@@]([H])(CC[C@]([H])(CCc2ccccc2)O)[C@@]([H])(C[C@]1([H])O)O)/CCCC(=O)OCCCCON(=O)=O

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

HIDE SMILES / InChI

Molecular Formula C27H41NO8
Molecular Weight 507.6174
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 5 / 5
E/Z Centers 1
Optical Activity UNSPECIFIED

Description
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

Latanoprost (free acid) is a metabolite of latanoprost which has been approved for use as an ocular hypotensive drug. Latanoprost is an isopropyl ester prodrug which is converted to the Latanoprost-acid by endogenous esterase enzymes. The free acid is pharmacologically active and is 200 times more potent than latanoprost as an agonist of the human recombinant Prostaglandin F receptor. However, the free Latanoprost-acid is more irritating and less effective than Latanoprost when applied directly to the eyes of human glaucoma patients.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P43088
Gene ID: 5737.0
Gene Symbol: PTGFR
Target Organism: Homo sapiens (Human)
3.6 nM [EC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
VYZULTA

Approved Use

VYZULTA is a prostaglandin analog indicated for the reduction of intraocular pressure in patients with open-angle glaucoma or ocular hypertension

Launch Date

1.48668482E12
Primary
VYZULTA

Approved Use

VYZULTA is a prostaglandin analog indicated for the reduction of intraocular pressure in patients with open-angle glaucoma or ocular hypertension

Launch Date

1.48668482E12
Primary
VYZULTA

Approved Use

YZULTA™ (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 Date

1.50949436E12
Primary
VYZULTA

Approved Use

YZULTA™ (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 Date

1.50949436E12
Palliative
XALATAN

Approved Use

XALATAN Sterile Ophthalmic Solution is indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension.

Launch Date

8.3393282E11
Primary
XALATAN

Approved Use

XALATAN Sterile Ophthalmic Solution is indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension.

Launch Date

8.3393282E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
53 pg/mL
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

AUC

ValueDoseCo-administeredAnalytePopulation
7.15 ng × h/mL
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
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

T1/2

ValueDoseCo-administeredAnalytePopulation
16.6 min
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
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

Doses

DosePopulationAdverse 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%)
Meibomianitis (grade 1, 0.3%)
Sources:
11 ug/kg multiple, topical
MTD
unhealthy
10 ug/kg single, intravenous (max)
Overdose
Dose: 10 ug/kg
Route: intravenous
Route: single
Dose: 10 ug/kg
Sources:
healthy
Other AEs: Abdominal pain, Dizziness...
Other AEs:
Abdominal pain
Dizziness
Fatigue
Hot flushes
Nausea
Sweating
Sources:
AEs

AEs

AESignificanceDosePopulation
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
Dizziness
10 ug/kg single, intravenous (max)
Overdose
Dose: 10 ug/kg
Route: intravenous
Route: single
Dose: 10 ug/kg
Sources:
healthy
Fatigue
10 ug/kg single, intravenous (max)
Overdose
Dose: 10 ug/kg
Route: intravenous
Route: single
Dose: 10 ug/kg
Sources:
healthy
Hot flushes
10 ug/kg single, intravenous (max)
Overdose
Dose: 10 ug/kg
Route: intravenous
Route: single
Dose: 10 ug/kg
Sources:
healthy
Nausea
10 ug/kg single, intravenous (max)
Overdose
Dose: 10 ug/kg
Route: intravenous
Route: single
Dose: 10 ug/kg
Sources:
healthy
Sweating
10 ug/kg single, intravenous (max)
Overdose
Dose: 10 ug/kg
Route: intravenous
Route: single
Dose: 10 ug/kg
Sources:
healthy
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Interaction of PhXA41, a new prostaglandin analogue, with pilocarpine. A study on patients with elevated intraocular pressure.
1993 May
Corneal permeability to and ocular metabolism of phenyl substituted prostaglandin esters in vitro.
1994 Apr
Additive effect of latanoprost, a prostaglandin F2 alpha analogue, and timolol in patients with elevated intraocular pressure.
1994 Dec
A comparison of latanoprost and timolol in primary open-angle glaucoma and ocular hypertension. A 12-week study.
1996 Aug
Comparison of latanoprost and timolol in patients with ocular hypertension and glaucoma: a six-month masked, multicenter trial in the United States. The United States Latanoprost Study Group.
1996 Jan
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
Additive ocular hypotensive effect of latanoprost and acetazolamide. A short-term study in patients with elevated intraocular pressure.
1997 Sep
Effects of latanoprost and dipivefrin, alone or combined, on intraocular pressure and on blood-aqueous barrier permeability.
1998 Apr
Comparison of the effect of latanoprost 0.005% and timolol 0.5% on the calculated ocular perfusion pressure in patients with normal-tension glaucoma.
1998 May
The utilization of recombinant prostanoid receptors to determine the affinities and selectivities of prostaglandins and related analogs.
2000 Jan 17
Microvascular effects of selective prostaglandin analogues in the eye with special reference to latanoprost and glaucoma treatment.
2000 Jul
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
Diurnal intraocular pressure reduction with latanoprost 0.005% compared to timolol maleate 0.5% as monotherapy in subjects with exfoliation glaucoma.
2004 Sep
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
24-Hour control with a latanoprost-timolol fixed combination vs timolol alone.
2006 Nov
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
Efficacy and safety of latanoprost versus pilocarpine/timolol maleate fixed combination in patients with primary open-angle glaucoma or ocular hypertension.
2008 Dec
Comparison of the 24-hour intraocular pressure-lowering effects of latanoprost and dorzolamide/timolol fixed combination after 2 and 6 months of treatment.
2008 Jan
The prostaglandin transporter OATP2A1 is expressed in human ocular tissues and transports the antiglaucoma prostanoid latanoprost.
2010 May
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
2013 Nov
Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis.
2015 May 18
Latanoprostene Bunod 0.024% in Subjects With Open-angle Glaucoma or Ocular Hypertension: Pooled Phase 3 Study Findings.
2018 Jan
Patents

Sample Use Guides

One drop in the affected eye(s) once daily in the evening
Route of Administration: Other
HTMCs were seeded in 6-well plates at 2 x 10^5 cells/well in complete medium. When cells were confluent, they were incubated in low-serum medium overnight. Cells were pretreated with the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX; 100 mkM) for 30 minutes and then exposed to LBN (Latanoprostene bunod) or latanoprost for 30 minutes. The NO donor SE 175 (100 mkM) was used as a positive control. Cells were treated with IBMX (100 mkM) plus the NO-independent activator of soluble guanylyl cyclase (sGC) 3-(5-hydroxymethyl-2-furyl)-benzylindazole (YC-1; 10 mkM) in conjunction with the drug and/or NO donor treatments. To determine the role of sGC in NO-induced cGMP elevation, cells were also preincubated with the sGC inhibitor ODQ (1 mkM) for 30 minutes. After the incubation period, cells were harvested. A cGMP enzyme immunoassay (Enzo Life Sciences, Farmingdale, NY, USA) was performed with the cell lysates. LBN (1–100 mkM) significantly increased cGMP levels in a dose-dependent manner, with a half maximal effective concentration (EC50) of 1.5 6 1.3 mkM, and with maximal effect similar to that of 100 mkM SE 175.
Substance Class Chemical
Created
by admin
on Sat Jun 26 08:47:20 UTC 2021
Edited
by admin
on Sat Jun 26 08:47:20 UTC 2021
Record UNII
I6393O0922
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LATANOPROSTENE BUNOD
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
PF-3187207
Code English
BOL-303259-X
Code English
LATANOPROSTENE BUNOD [WHO-DD]
Common Name English
VYZULTA
Brand Name English
NCX 116
Code English
LATANOPROSTENE BUNOD [INN]
Common Name English
LATANOPROSTENE BUNOD [ORANGE BOOK]
Common Name English
4-(NITROOXY)BUTYL (5Z)-7-((1R,2R,3R,5S)-3,5-DIHYDROXY-2-((3R)-3-HYDROXY-5-PHENYLPENTYL)CYCLOPENTYL)HEPT-5-ENOATE
Systematic Name English
LATANOPROSTENE BUNOD [MI]
Common Name English
LATANOPROSTENE BUNOD [USAN]
Common Name English
NCX-116
Code English
Code System Code Type Description
DRUG CENTRAL
5261
Created by admin on Sat Jun 26 08:47:20 UTC 2021 , Edited by admin on Sat Jun 26 08:47:20 UTC 2021
PRIMARY
FDA UNII
I6393O0922
Created by admin on Sat Jun 26 08:47:20 UTC 2021 , Edited by admin on Sat Jun 26 08:47:20 UTC 2021
PRIMARY
DRUG BANK
DB11660
Created by admin on Sat Jun 26 08:47:20 UTC 2021 , Edited by admin on Sat Jun 26 08:47:20 UTC 2021
PRIMARY
RXCUI
1988390
Created by admin on Sat Jun 26 08:47:20 UTC 2021 , Edited by admin on Sat Jun 26 08:47:20 UTC 2021
PRIMARY
LACTMED
Latanoprostene Bunod
Created by admin on Sat Jun 26 08:47:20 UTC 2021 , Edited by admin on Sat Jun 26 08:47:20 UTC 2021
PRIMARY
PUBCHEM
11156438
Created by admin on Sat Jun 26 08:47:20 UTC 2021 , Edited by admin on Sat Jun 26 08:47:20 UTC 2021
PRIMARY
INN
9629
Created by admin on Sat Jun 26 08:47:20 UTC 2021 , Edited by admin on Sat Jun 26 08:47:20 UTC 2021
PRIMARY
CAS
860005-21-6
Created by admin on Sat Jun 26 08:47:20 UTC 2021 , Edited by admin on Sat Jun 26 08:47:20 UTC 2021
PRIMARY
ChEMBL
CHEMBL2364612
Created by admin on Sat Jun 26 08:47:20 UTC 2021 , Edited by admin on Sat Jun 26 08:47:20 UTC 2021
PRIMARY
NCI_THESAURUS
C170095
Created by admin on Sat Jun 26 08:47:20 UTC 2021 , Edited by admin on Sat Jun 26 08:47:20 UTC 2021
PRIMARY
MERCK INDEX
M12042
Created by admin on Sat Jun 26 08:47:20 UTC 2021 , Edited by admin on Sat Jun 26 08:47:20 UTC 2021
PRIMARY
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