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: http://www.drugbank.ca/drugs/DB00287doi: 10.1080/00480169.1974.34145
Curator's Comment: description was created based on several sources, including: https://www.ncbi.nlm.nih.gov/pubmed/12490597 | https://www.ncbi.nlm.nih.gov/pubmed/8921038

(+)-Fluprostenol is the optically active enantiomer of fluprostenol. It is a potent and highly selective prostaglandin F2-alpha (FP) receptor agonist. (+)-Fluprostenol corrected corpora lutea persistence in the mares without significant clinical side effects. It was also an effective at inducing parturition in alpacas.

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 2678		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 2678		49.9 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Open-angle glaucoma 51 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021994s000_LBL.pdf	Primary	Approved 8429	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
0.018 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
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

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
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
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

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 n = 1 Health Status: unhealthy Sex: F Population Size: 1 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 n = 336 Health Status: unhealthy Population Size: 336 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 n = 1 Health Status: unhealthy Sex: F Population Size: 1 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 n = 1 Health Status: unhealthy Sex: F Population Size: 1 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 n = 336 Health Status: unhealthy Population Size: 336 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 n = 336 Health Status: unhealthy Population Size: 336 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 n = 336 Health Status: unhealthy Population Size: 336 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 n = 336 Health Status: unhealthy Population Size: 336 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 72

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
esterase 72	substrate 3367 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
MolPort	MolPort-006-167-507	https://www.molport.com/shop/molecule-link/MolPort-006-167-507
ZINC	ZINC000004474682	http://zinc15.docking.org/substances/ZINC000004474682
eMolecules	26757104	https://www.emolecules.com/cgi-bin/more?vid=26757104

PubMed

Title	Date	PubMed
Serum and urinary vascular endothelial growth factor levels in non-small cell lung cancer patients.	1996 Dec	9038626
Ligand binding specificities of the eight types and subtypes of the mouse prostanoid receptors expressed in Chinese hamster ovary cells.	1997 Sep	9313928
The utilization of recombinant prostanoid receptors to determine the affinities and selectivities of prostaglandins and related analogs.	2000 Jan 17	10634944
The comparative cardiovascular, pulmonary, ocular blood flow, and ocular hypotensive effects of topical travoprost, bimatoprost, brimonidine, and betaxolol.	2004 Aug	15321024
Prostaglandins differently regulate FGF-2 and FGF receptor expression and induce nuclear translocation in osteoblasts via MAPK kinase.	2005 Feb	15654655
Mechanism of action of bimatoprost, latanoprost, and travoprost in healthy subjects. A crossover study.	2008 May	18452763
Update on the mechanism of action of topical prostaglandins for intraocular pressure reduction.	2008 Nov	19038618
Prostanoids for the management of glaucoma.	2008 Nov	18983226
A case of melancholic depression induced by beta-blocker antiglaucoma agents.	2008 Oct 6	18837686
Outcome of raised intraocular pressure in uveitic eyes with and without a corticosteroid-induced hypertensive response.	2009 Aug	19403113
Pharmacotherapy of intraocular pressure - part II. Carbonic anhydrase inhibitors, prostaglandin analogues and prostamides.	2009 Dec	19929706
Niacin promotes adipogenesis by reducing production of anti-adipogenic PGF2α through suppression of C/EBPβ-activated COX-2 expression.	2011 Apr	21236357

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dosage is one drop in the affected eye(s) once daily in the evening. TRAVATAN Z® (travoprost ophthalmic solution) should not be administered more than once daily

Route of Administration: Topical

In Vitro Use Guide

Travoprost stimulated the contraction of isolated non-pregnant female rat uterus in a concentration-dependent manner with the agonist potency EC(50)=1.3+/-0.07 nM

Name

Type

Language

FLUPROSTENOL, (+)-

Common 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

AL-5848

Code

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