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

Details

Stereochemistry ABSOLUTE
Molecular Formula C26H40O5
Molecular Weight 432.5928
Optical Activity UNSPECIFIED
Defined Stereocenters 5 / 5
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of LATANOPROST, (5E)-

SMILES

CC(C)OC(=O)CCC\C=C\C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1CC[C@@H](O)CCC2=CC=CC=C2

InChI

InChIKey=GGXICVAJURFBLW-RDSJPUOVSA-N
InChI=1S/C26H40O5/c1-19(2)31-26(30)13-9-4-3-8-12-22-23(25(29)18-24(22)28)17-16-21(27)15-14-20-10-6-5-7-11-20/h3,5-8,10-11,19,21-25,27-29H,4,9,12-18H2,1-2H3/b8-3+/t21-,22+,23+,24-,25+/m0/s1

HIDE SMILES / InChI

Molecular Formula C26H40O5
Molecular Weight 432.5928
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

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

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
Effects of latanoprost and dipivefrin, alone or combined, on intraocular pressure and on blood-aqueous barrier permeability.
1998 Apr
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
A comparison of latanoprost monotherapy with a combination therapy of timolol/dorzolamide in patients with primary open-angle glaucoma.
2006 Summer
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
Outcome of raised intraocular pressure in uveitic eyes with and without a corticosteroid-induced hypertensive response.
2009 Aug
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

In Vivo Use Guide
Unknown
Route of Administration: Unknown
In Vitro Use Guide
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 Thu Jul 06 20:16:04 UTC 2023
Edited
by admin
on Thu Jul 06 20:16:04 UTC 2023
Record UNII
ZC39I2T1VW
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LATANOPROST, (5E)-
Common Name English
TRANS-LATANOPROST
Common Name English
LATANOPROST IMPURITY F [EP IMPURITY]
Common Name English
ISOPROPYL (E)-7-((1R,2R,3R,5S)-3,5-DIHYDROXY-2-((3R)-3-HYDROXY-5-PHENYLPENTYL)CYCLOPENTYL)-5-HEPTENOATE
Systematic Name English
5,6-TRANS-LATANOPROST
Common Name English
LATANOPROST RELATED COMPOUND A [USP-RS]
Common Name English
LATANOPROST RELATED COMPOUND A [USP IMPURITY]
Common Name English
5-HEPTENOIC ACID, 7-((1R,2R,3R,5S)-3,5-DIHYDROXY-2-((3R)-3-HYDROXY-5-PHENYLPENTYL)CYCLOPENTYL)-, 1-METHYLETHYL ESTER, (5E)-
Systematic Name English
Code System Code Type Description
RS_ITEM_NUM
1357486
Created by admin on Thu Jul 06 20:16:04 UTC 2023 , Edited by admin on Thu Jul 06 20:16:04 UTC 2023
PRIMARY
PUBCHEM
5282380
Created by admin on Thu Jul 06 20:16:04 UTC 2023 , Edited by admin on Thu Jul 06 20:16:04 UTC 2023
PRIMARY
CAS
913258-34-1
Created by admin on Thu Jul 06 20:16:04 UTC 2023 , Edited by admin on Thu Jul 06 20:16:04 UTC 2023
PRIMARY
FDA UNII
ZC39I2T1VW
Created by admin on Thu Jul 06 20:16:04 UTC 2023 , Edited by admin on Thu Jul 06 20:16:04 UTC 2023
PRIMARY
Related Record Type Details
PARENT -> IMPURITY
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
PARENT -> IMPURITY
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP