FLUPROSTENOL, (+)-

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C23H29F3O6
Molecular Weight	458.468
Optical Activity	( + )
Defined Stereocenters	5 / 5
E/Z Centers	2
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O[C@@H](COC1=CC(=CC=C1)C(F)(F)F)\C=C\[C@H]2[C@H](O)C[C@H](O)[C@@H]2C\C=C/CCCC(O)=O

InChI

InChIKey=WWSWYXNVCBLWNZ-QIZQQNKQSA-N

InChI=1S/C23H29F3O6/c24-23(25,26)15-6-5-7-17(12-15)32-14-16(27)10-11-19-18(20(28)13-21(19)29)8-3-1-2-4-9-22(30)31/h1,3,5-7,10-12,16,18-21,27-29H,2,4,8-9,13-14H2,(H,30,31)/b3-1-,11-10+/t16-,18-,19-,20+,21-/m1/s1

HIDE SMILES / InChI

Description
Sources: doi: 10.1080/00480169.1974.34145http://www.drugbank.ca/drugs/DB00287
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021994s000_LBL.pdf

Travoprost, an isopropyl ester prodrug, is a synthetic prostaglandin F2 alpha analogue that is rapidly hydrolyzed by esterases in the cornea to its biologically active free acid. The travoporst free acid is potent and highly selective for the FP prostanoid receptor. Travoprost free acid is a selective FP prostanoid receptor agonist and is believed to reduce intraocular pressure by increasing the drainage of aqueous humor, which is done primarily through increased uveoscleral outflow and to a lesser extent, trabecular outflow facility. Travoprost ophthalmic solution is used for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension who are intolerant of other intraocular pressure lowering medications or insufficiently responsive (failed to achieve target IOP determined after multiple measurements over time) to another intraocular pressure lowering medication. Travoprost is known by the brand names of Travatan and Travatan Z, manufactured by Alcon.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Prostanoid FP receptor 21 Target ID: CHEMBL1987 Sources: http://www.drugbank.ca/drugs/DB00287 \| http://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021994s000_LBL.pdf	Agonist 2752		1.4 nM [EC50]
Prostanoid FP receptor 21 Target ID: CHEMBL1987 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12556403 \| https://www.ncbi.nlm.nih.gov/pubmed/12490597	Agonist 2752		49.9 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Open-angle glaucoma 53 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021994s000_LBL.pdf	Primary	Approved 8583	TRAVATAN Z Approved Use TRAVATAN Z® (travoprost ophthalmic solution) 0.004% is indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. Launch Date 2006
Infertility 14 Sources: DOI: 10.1080/00480169.1974.34145 https://www.ncbi.nlm.nih.gov/pubmed/6911921	Primary	Preclinical	Unknown Approved Use Unknown
Labor delay 3 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8921038	Preventing	Preclinical	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
0.049 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28437175	1 drop 1 times / day multiple, ocular dose: 1 drop route of administration: Ocular experiment type: MULTIPLE co-administered:		FLUPROSTENOL plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN
0.018 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021994lbl.pdf	1 drop 1 times / day multiple, ocular dose: 1 drop route of administration: Ocular experiment type: MULTIPLE co-administered:		FLUPROSTENOL plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
0.039 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28437175	1 drop 1 times / day multiple, ocular dose: 1 drop route of administration: Ocular experiment type: MULTIPLE co-administered:		FLUPROSTENOL plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
31.8 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28437175	1 drop 1 times / day multiple, ocular dose: 1 drop route of administration: Ocular experiment type: MULTIPLE co-administered:		FLUPROSTENOL plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN
45 min DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021994lbl.pdf	1 drop 1 times / day multiple, ocular dose: 1 drop route of administration: Ocular experiment type: MULTIPLE co-administered:		FLUPROSTENOL plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
20% REVIEW https://www.ema.europa.eu/en/documents/scientific-discussion/travatan-epar-scientific-discussion_en.pdf			FLUPROSTENOL plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
0.004 % 1 times / 15 min multiple, ophthalmic Overdose Dose: 0.004 %, 1 times / 15 min Route: ophthalmic Route: multiple Dose: 0.004 %, 1 times / 15 min Sources: https://pubmed.ncbi.nlm.nih.gov/25259759	unhealthy Health Status: unhealthy Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/25259759	Disc. AE: Abdominal cramps, Bleeding menstrual heavy... AEs leading to discontinuation/dose reduction: Abdominal cramps (severe, 1 patient) Bleeding menstrual heavy (severe, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/25259759
0.004 % 1 times / day multiple, ophthalmic Recommended Dose: 0.004 %, 1 times / day Route: ophthalmic Route: multiple Dose: 0.004 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2001/21257lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2001/21257lbl.pdf	Disc. AE: Conjunctival hyperemia... AEs leading to discontinuation/dose reduction: Conjunctival hyperemia (3%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2001/21257lbl.pdf
0.004 % 1 times / day multiple, ophthalmic Recommended Dose: 0.004 %, 1 times / day Route: ophthalmic Route: multiple Dose: 0.004 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021994s000_MedR.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021994s000_MedR.pdf	Disc. AE: Hyperemia eye, Iritis... AEs leading to discontinuation/dose reduction: Hyperemia eye (2 patients) Iritis (1 patient) Dermatitis (1 patient) Upper respiratory infection (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021994s000_MedR.pdf

AEs

AE	Significance	Dose	Population
Abdominal cramps	severe, 1 patient Disc. AE	0.004 % 1 times / 15 min multiple, ophthalmic Overdose Dose: 0.004 %, 1 times / 15 min Route: ophthalmic Route: multiple Dose: 0.004 %, 1 times / 15 min Sources: https://pubmed.ncbi.nlm.nih.gov/25259759	unhealthy Health Status: unhealthy Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/25259759
Bleeding menstrual heavy	severe, 1 patient Disc. AE	0.004 % 1 times / 15 min multiple, ophthalmic Overdose Dose: 0.004 %, 1 times / 15 min Route: ophthalmic Route: multiple Dose: 0.004 %, 1 times / 15 min Sources: https://pubmed.ncbi.nlm.nih.gov/25259759	unhealthy Health Status: unhealthy Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/25259759
Conjunctival hyperemia	3% Disc. AE	0.004 % 1 times / day multiple, ophthalmic Recommended Dose: 0.004 %, 1 times / day Route: ophthalmic Route: multiple Dose: 0.004 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2001/21257lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2001/21257lbl.pdf
Dermatitis	1 patient Disc. AE	0.004 % 1 times / day multiple, ophthalmic Recommended Dose: 0.004 %, 1 times / day Route: ophthalmic Route: multiple Dose: 0.004 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021994s000_MedR.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021994s000_MedR.pdf
Iritis	1 patient Disc. AE	0.004 % 1 times / day multiple, ophthalmic Recommended Dose: 0.004 %, 1 times / day Route: ophthalmic Route: multiple Dose: 0.004 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021994s000_MedR.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021994s000_MedR.pdf
Upper respiratory infection	1 patient Disc. AE	0.004 % 1 times / day multiple, ophthalmic Recommended Dose: 0.004 %, 1 times / day Route: ophthalmic Route: multiple Dose: 0.004 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021994s000_MedR.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021994s000_MedR.pdf
Hyperemia eye	2 patients Disc. AE	0.004 % 1 times / day multiple, ophthalmic Recommended Dose: 0.004 %, 1 times / day Route: ophthalmic Route: multiple Dose: 0.004 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021994s000_MedR.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021994s000_MedR.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	esterase 74

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
esterase 74	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21257_Travatan_biopharmr.pdf#page=10	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:746859	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:746859
ChemicalBook	CB5703458	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB5703458
eMolecules	26757104	https://www.emolecules.com/cgi-bin/more?vid=26757104
MolPort	MolPort-006-167-507	https://www.molport.com/shop/molecule-link/MolPort-006-167-507
ZINC	ZINC000004474682	http://zinc15.docking.org/substances/ZINC000004474682

PubMed

Title	Date	PubMed
Niacin promotes adipogenesis by reducing production of anti-adipogenic PGF2α through suppression of C/EBPβ-activated COX-2 expression.	2011-04	21236357
Pharmacotherapy of intraocular pressure - part II. Carbonic anhydrase inhibitors, prostaglandin analogues and prostamides.	2009-12	19929706
Outcome of raised intraocular pressure in uveitic eyes with and without a corticosteroid-induced hypertensive response.	2009-08	19403113
Update on the mechanism of action of topical prostaglandins for intraocular pressure reduction.	2008-11	19038618
Prostanoids for the management of glaucoma.	2008-11	18983226
A case of melancholic depression induced by beta-blocker antiglaucoma agents.	2008-10-06	18837686
Mechanism of action of bimatoprost, latanoprost, and travoprost in healthy subjects. A crossover study.	2008-05	18452763
Prostaglandins differently regulate FGF-2 and FGF receptor expression and induce nuclear translocation in osteoblasts via MAPK kinase.	2005-02	15654655
The comparative cardiovascular, pulmonary, ocular blood flow, and ocular hypotensive effects of topical travoprost, bimatoprost, brimonidine, and betaxolol.	2004-08	15321024
The utilization of recombinant prostanoid receptors to determine the affinities and selectivities of prostaglandins and related analogs.	2000-01-17	10634944
Ligand binding specificities of the eight types and subtypes of the mouse prostanoid receptors expressed in Chinese hamster ovary cells.	1997-09	9313928
Serum and urinary vascular endothelial growth factor levels in non-small cell lung cancer patients.	1996-12	9038626

Patents

Sample Use Guides

In Vivo Use Guide

Mare: single dose - 263 ug in 5 ml

Route of Administration: Intramuscular

In Vitro Use Guide

FP-receptor-mediated phosphoinositide (PI) turnover and [Ca(2+)](i) mobilization were measured in human trabecular meshwork (h-TM) cells by determining the accumulation of [(3)H]-inositol phosphates ([(3)H]-IPs). Travoprost acid concentration-dependently stimulated production of [(3)H]-IPs in h-TM cells with the following agonist potency EC(50) = 2.4 nM

Name

Type

Language

FLUPROSTENOL, (+)-

Common Name

English

AL-5848

Preferred Name

English

TRAVOPROST RELATED COMPOUND A [USP IMPURITY]

Common Name

English

(+)-FLUPROSTENOL

Common Name

English

(5Z ,13E )-(9S,11R,15R )-9,11,15-TRIHYDROXY-16-(M-TRIFLUOROMETHYLPHENOXY)-17,18,19,20-TETRANOR-5,13-PROSTADIENOIC ACID

Common Name

English

16-(M-TRIFLUOROMETHYLPHENOXY)-17,18,19,20-TETRANORPROSTAGLANDIN F2.ALPHA.

Systematic Name

English

TRAVOPROST ACID

Common Name

English

TRAVOPROST RELATED COMPOUND A [USP-RS]

Common Name

English

5-HEPTENOIC ACID, 7-((1R,2R,3R,5S)-3,5-DIHYDROXY-2-((1E,3R)-3-HYDROXY-4-(3-(TRIFLUOROMETHYL)PHENOXY)-1-BUTEN-1-YL)CYCLOPENTYL)-, (5Z)-

Systematic Name

English

TRAVOPROST RELATED COMPOUND A

Common Name

English

Code System Code Type Description

CAS

54276-17-4