LATANOPROSTENE BUNOD

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

Structure Search

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

HIDE SMILES / InChI

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

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020597s045s048lbl.pdfhttps://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207795Orig1s000lbl.pdfhttps://www.ncbi.nlm.nih.gov/pubmed/9698288 | https://www.ncbi.nlm.nih.gov/pubmed/21788077
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.

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 2662	3.6 nM [EC50]
Prostanoid FP receptor 21 Target ID: CHEMBL1987 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9733584	Agonist 2662
Prostanoid FP receptor 21 Target ID: CHEMBL1987 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207795Orig1s000lbl.pdf	Agonist 2662

Conditions

Condition	Modality	Highest Phase	Product
Open-angle glaucoma 51 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207795Orig1s000lbl.pdf	Primary	Approved 8360	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
Ocular hypertension 50 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207795Orig1s000lbl.pdf	Primary	Approved 8360	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
Open-angle glaucoma 51 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207795Orig1s000lbl.pdf	Primary	Approved 8360	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
Ocular hypertension 50 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207795Orig1s000lbl.pdf	Primary	Approved 8360	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
Open-angle glaucoma 51 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020597s045s048lbl.pdf	Palliative	Approved 8360	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
Ocular hypertension 50 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020597s045s048lbl.pdf	Primary	Approved 8360	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

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 266 OATP2B1 103 MRP1 106 MRP2 201 MRP5 40 P-gp 1527 BCRP 555	CYP450 32

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP450 41	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/020597Orig1s000rev.pdf#page=342 Page: 342.0	unlikely
CYP450 41	inhibitor 3240 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 266	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/207795Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
P-gp 1527	substrate 3326 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3096535/	no
BCRP 555	substrate 3326 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3096535/	unlikely
OATP2B1 103	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/20019365/ Page: 6.0	weak
MRP1 106	substrate 3326 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3096535/	yes
MRP2 201	substrate 3326 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3096535/	yes
MRP5 40	substrate 3326 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
Corneal permeability to and ocular metabolism of phenyl substituted prostaglandin esters in vitro.	1994 Apr	8022849
Additive effect of latanoprost, a prostaglandin F2 alpha analogue, and timolol in patients with elevated intraocular pressure.	1994 Dec	7819171
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
A randomized, comparative open-label study on the efficacy of latanoprost and timolol in steroid induced ocular hypertension after photorefractive keratectomy.	2000 Jul-Sep	11071027
Syncope and falls due to timolol eye drops.	2006 Apr 22	16627515
Comparison of the effects of bimatoprost and a fixed combination of latanoprost and timolol on circadian intraocular pressure.	2007 Dec	17459480
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	18166407
Outcome of raised intraocular pressure in uveitic eyes with and without a corticosteroid-induced hypertensive response.	2009 Aug	19403113
Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis.	2015 May 18	25811541
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 `Thu Jul 06 09:58:14 UTC 2023` Edited by `admin` on `Thu Jul 06 09:58:14 UTC 2023`
Record UNII	I6393O0922
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

LATANOPROSTENE BUNOD

Official Name

English

PF-3187207

Code

English

BOL-303259-X

Code

English

Latanoprostene bunod [WHO-DD]

Common Name

English

VYZULTA

Brand Name

English

NCX116

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

WIKIPEDIA

Latanoprostene bunod