LATANOPROST

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 Search

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

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	5 / 5
E/Z Centers	1
Optical Activity	UNSPECIFIED

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020597s045s048lbl.pdfhttps://www.ncbi.nlm.nih.gov/pubmed/9698288 | https://www.ncbi.nlm.nih.gov/pubmed/21788077https://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.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Prostaglandin F2-alpha receptor 12 Target ID: P43088 Gene ID: 5737.0 Gene Symbol: PTGFR Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/10634944	Agonist 2678	3.6 nM [EC50]
Prostanoid FP receptor 21 Target ID: CHEMBL1987 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9733584	Agonist 2678
Prostanoid FP receptor 21 Target ID: CHEMBL1987 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207795Orig1s000lbl.pdf	Agonist 2678

Conditions

Condition	Modality	Highest Phase	Product
Open-angle glaucoma 51 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207795Orig1s000lbl.pdf	Primary	Approved 8429	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 2017
Ocular hypertension 50 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207795Orig1s000lbl.pdf	Primary	Approved 8429	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 2017
Open-angle glaucoma 51 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207795Orig1s000lbl.pdf	Primary	Approved 8429	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 2017
Ocular hypertension 50 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207795Orig1s000lbl.pdf	Primary	Approved 8429	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 2017
Open-angle glaucoma 51 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020597s045s048lbl.pdf	Palliative	Approved 8429	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 1996
Ocular hypertension 50 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020597s045s048lbl.pdf	Primary	Approved 8429	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 1996

C_max

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

T_1/2

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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/206185Orig1s000StatR.pdf	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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/206185Orig1s000StatR.pdf	Disc. AE: Iritis, Meibomianitis... AEs leading to discontinuation/dose reduction: Iritis (grade 2, 0.3%) Meibomianitis (grade 1, 0.3%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/206185Orig1s000StatR.pdf
11 ug/kg multiple, topical MTD Dose: 11 ug/kg Route: topical Route: multiple Dose: 11 ug/kg Sources: https://www.ema.europa.eu/en/documents/referral/xalatan-article-29-paediatrics-chmp-assessment-report_en.pdf	unhealthy Health Status: unhealthy Sources: https://www.ema.europa.eu/en/documents/referral/xalatan-article-29-paediatrics-chmp-assessment-report_en.pdf	Sources: https://www.ema.europa.eu/en/documents/referral/xalatan-article-29-paediatrics-chmp-assessment-report_en.pdf
10 ug/kg single, intravenous (max) Overdose Dose: 10 ug/kg Route: intravenous Route: single Dose: 10 ug/kg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020597s052lbl.pdf	healthy Health Status: healthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020597s052lbl.pdf	Other AEs: Abdominal pain, Dizziness... Other AEs: Abdominal pain Dizziness Fatigue Hot flushes Nausea Sweating Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020597s052lbl.pdf

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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/206185Orig1s000StatR.pdf	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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/206185Orig1s000StatR.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/206185Orig1s000StatR.pdf	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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/206185Orig1s000StatR.pdf
Abdominal pain		10 ug/kg single, intravenous (max) Overdose Dose: 10 ug/kg Route: intravenous Route: single Dose: 10 ug/kg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020597s052lbl.pdf	healthy Health Status: healthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020597s052lbl.pdf
Dizziness		10 ug/kg single, intravenous (max) Overdose Dose: 10 ug/kg Route: intravenous Route: single Dose: 10 ug/kg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020597s052lbl.pdf	healthy Health Status: healthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020597s052lbl.pdf
Fatigue		10 ug/kg single, intravenous (max) Overdose Dose: 10 ug/kg Route: intravenous Route: single Dose: 10 ug/kg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020597s052lbl.pdf	healthy Health Status: healthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020597s052lbl.pdf
Hot flushes		10 ug/kg single, intravenous (max) Overdose Dose: 10 ug/kg Route: intravenous Route: single Dose: 10 ug/kg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020597s052lbl.pdf	healthy Health Status: healthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020597s052lbl.pdf
Nausea		10 ug/kg single, intravenous (max) Overdose Dose: 10 ug/kg Route: intravenous Route: single Dose: 10 ug/kg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020597s052lbl.pdf	healthy Health Status: healthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020597s052lbl.pdf
Sweating		10 ug/kg single, intravenous (max) Overdose Dose: 10 ug/kg Route: intravenous Route: single Dose: 10 ug/kg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020597s052lbl.pdf	healthy Health Status: healthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020597s052lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP450 25	CYP 270 OATP2B1 104 MRP1 107 MRP2 205 MRP5 40 P-gp 1537 BCRP 561	CYP450 32

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP450 41	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/020597Orig1s000rev.pdf#page=342 Page: 342.0	unlikely
CYP450 41	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/020597Orig1s000rev.pdf#page=342 Page: 342.0	unlikely

Drug as victim

Target	Modality	Activity
CYP 270	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207795Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
P-gp 1537	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3096535/	no
BCRP 561	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3096535/	unlikely
OATP2B1 104	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/20019365/ Page: 6.0	weak
MRP1 107	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3096535/	yes
MRP2 205	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3096535/	yes
MRP5 40	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3096535/	yes

Sourcing

Vendor/Aggregator	ID	URL
AA Blocks	AA00BXFY	https://www.aablocks.com/goods/Goods/detail?id=AA00BXFY
AK Scientific, Inc. (AKSCI)	Z6154	http://www.aksci.com/item_detail.php?cat=Z6154
Aaron Chemicals	AR00BY7Q	http://www.aaronchem.com/41639-83-2
Achemtek	0104-022891	http://www.achemtek.com/41639-83-2
Alfa Chemistry	AP41639832-B	https://reagents.alfa-chemistry.com/product/latanoprost-acid-cas-41639-83-2-11265.html
Alfa Chemistry	AP41639832-A	https://reagents.alfa-chemistry.com/product/latanoprost-related-compound-e-cas-41639-83-2-11264.html
Ambinter	Amb15690628	http://www.ambinter.com/reference/15690628
Aurora Fine Chemicals LLC	A17.898.261	http://online.aurorafinechemicals.com/info?ID=A17.898.261
AvaChem Scientific	2038	http://www.avachem.com/productSearch.asp?2038
Chem Scene	CS-0068357	http://www.chemscene.com/41639-83-2.html
ChemMol	99087782	http://www.chemmol.com/chemmol/99087782.html
Chemspace	CSSB00020648370	https://chem-space.com/CSSB00020648370
Glentham Life Sciences	GL6689	http://www.glentham.com/products/product/GL6689/
Lab Network	LN01304996	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01304996
MedChem Express	HY-113756A	https://www.medchemexpress.com/latanoprost-acid.html
OChem	18671	http://www.ocheminc.com/index.php?act=psearch&pid=639L832
Sigma-Aldrich	L1292_SIGMA	https://www.sigmaaldrich.com/catalog/product/sigma/l1292?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	1357533_USP	https://www.sigmaaldrich.com/catalog/product/usp/1357533?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Smolecule	S532544	http://www.smolecule.com/products/s532544
THE BioTek	bt-272608	https://www.thebiotek.com/product/inhibitors/bt-272608
eNovation Chemicals	D592348	https://www.enovationchem.com/ProductDetails.asp?ProductID=D592348
eNovation Chemicals	D758325	https://www.enovationchem.com/ProductDetails.asp?ProductID=D758325
iChemical	EBD26372	http://www.ichemical.com/products/41639-83-2.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs

PubMed

Title	Date	PubMed
Interaction of PhXA41, a new prostaglandin analogue, with pilocarpine. A study on patients with elevated intraocular pressure.	1993 May	8489450
Corneal permeability to and ocular metabolism of phenyl substituted prostaglandin esters in vitro.	1994 Apr	8022849
A comparison of latanoprost and timolol in primary open-angle glaucoma and ocular hypertension. A 12-week study.	1996 Aug	8694726
The lack of respiratory effects of the ocular hypotensive drug latanoprost in patients with moderate-steroid treated asthma.	1997 Feb	9154286
Additive ocular hypotensive effect of latanoprost and acetazolamide. A short-term study in patients with elevated intraocular pressure.	1997 Sep	9307648
Effects of latanoprost and dipivefrin, alone or combined, on intraocular pressure and on blood-aqueous barrier permeability.	1998 Apr	9640189
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	9625541
The utilization of recombinant prostanoid receptors to determine the affinities and selectivities of prostaglandins and related analogs.	2000 Jan 17	10634944
Microvascular effects of selective prostaglandin analogues in the eye with special reference to latanoprost and glaucoma treatment.	2000 Jul	10785618
Efficacy and safety of latanoprost versus pilocarpine/timolol maleate fixed combination in patients with primary open-angle glaucoma or ocular hypertension.	2008 Dec	18721251
Outcome of raised intraocular pressure in uveitic eyes with and without a corticosteroid-induced hypertensive response.	2009 Aug	19403113
Latanoprostene Bunod 0.024% in Subjects With Open-angle Glaucoma or Ocular Hypertension: Pooled Phase 3 Study Findings.	2018 Jan	29194198

Patents

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 Created by `admin` on `Fri Dec 15 15:39:37 GMT 2023` Edited by `admin` on `Fri Dec 15 15:39:37 GMT 2023`
Record UNII	6Z5B6HVF6O
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

LATANOPROST

Official Name

English

Isopropyl (Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(3R)-3-hydroxy-5-phenylpentyl]cyclopentyl]-5-heptenoate

Systematic Name

English

PHXA41

Code

English

LATANOPROST [MART.]

Common Name

English

5-HEPTENOIC ACID, 7-(3,5-DIHYDROXY-2-(3-HYDROXY-5-PHENYLPENTYL)CYCLOPENTYL)-1-METHYLETHYL ESTER, (1R-(1.ALPHA.(Z),2.BETA.(R*),3.ALPHA.,5.ALPHA.))-

Common Name

English

XA-41

Code

English

T2345

Code

English

T-2345

Code

English

LATANOPROST [ORANGE BOOK]

Common Name

English

latanoprost [INN]

Common Name

English

XELPROS

Brand Name

English

Latanoprost [WHO-DD]

Common Name

English

LATANOPROST COMPONENT OF ROCKLATAN

Common Name

English

XALATAN

Brand Name

English

LATANOPROST [MI]

Common Name

English

ROCKLATAN COMPONENT LATANOPROST

Common Name

English

LATANOPROST (ISOPROPYL ESTER)

Common Name

English

LATANOPROST [USAN]

Common Name

English

LATANOPROST [JAN]

Common Name

English

XA41

Code

English

LATANOPROST [USP-RS]

Common Name

English

IYUZEH

Brand Name

English

LATANOPROST [EP MONOGRAPH]

Common Name

English

LATANOPROST [USP MONOGRAPH]

Common Name

English

LATANOPROST [VANDF]

Common Name

English

PHXA-41

Code

English

XALACOM COMPONENT LATANOPROST

Brand Name

English

Classification Tree Code System Code

WHO-VATC

QS01EE01