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

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-CEYXHVGTSA-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
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 5 / 5
E/Z Centers 1
Optical Activity UNSPECIFIED

Description

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.

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
3.6 nM [EC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
VYZULTA
Primary
VYZULTA
Primary
VYZULTA
Primary
VYZULTA
Palliative
XALATAN
Primary
XALATAN

Cmax

ValueDoseCo-administeredAnalytePopulation
53 pg/mL
1.5 μg single, ocular
LATANOPROST ACID plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
7.15 ng × h/mL
3 μg/kg bw single, intravenous
LATANOPROST ACID plasma
Homo sapiens
34 pg × h/mL
1.5 μg single, ocular
LATANOPROST ACID plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
16.6 min
3 μg/kg bw single, intravenous
LATANOPROST ACID plasma
Homo sapiens
17 min
1.5 μg single, ocular
LATANOPROST ACID plasma
Homo sapiens

Doses

AEs

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer









Drug as perpetrator​

Drug as victim

PubMed

Sample Use Guides

In Vivo Use Guide
One drop in the affected eye(s) once daily in the evening.
Route of Administration: Other
In Vitro Use Guide
Latanoprost above concentrations of 3.125 mg/l can induce dose- and time-dependent morphological abnormality, growth retardation, viability decline, and plasma membrane permeability elevation of human corneal stromal (HCS) cells. Moreover, latanoprost can arrest the cell cycle of these cells at S phase and induce PS externalization, DNA fragmentation, and apoptotic body formation of the cells. Furthermore, latanoprost can induce activation of caspase-3, -8 and -9; disruption of MTP; downregulation of anti-apoptotic Bcl-2; upregulation of pro-apoptotic Bax; and cytoplasmic cytochrome c release
Substance Class Chemical
Record UNII
6Z5B6HVF6O
Record Status Validated (UNII)
Record Version