Tafluprost

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C25H34F2O5
Molecular Weight	452.5313
Optical Activity	( + )
Defined Stereocenters	4 / 4
E/Z Centers	2
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]1\C=C\C(F)(F)COC2=CC=CC=C2

InChI

InChIKey=WSNODXPBBALQOF-VEJSHDCNSA-N

InChI=1S/C25H34F2O5/c1-18(2)32-24(30)13-9-4-3-8-12-20-21(23(29)16-22(20)28)14-15-25(26,27)17-31-19-10-6-5-7-11-19/h3,5-8,10-11,14-15,18,20-23,28-29H,4,9,12-13,16-17H2,1-2H3/b8-3-,15-14+/t20-,21-,22+,23-/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15037111http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/202514s003s004lbl.pdf
Curator's Comment: http://www.merck.com/licensing/our-partnership/santen-partnership.html

Tafluprost acid is a prostanoid selective FP receptor agonist that is believed to reduce the intraocular pressure (IOP) by increasing the outflow of aqueous humor. Studies in animals and humans suggest that the main mechanism of action is increased uveoscleral outflow. A prostaglandin analogue ester prodrug used topically (as eye drops) to control the progression of glaucoma and in the management of ocular hypertension. Tafluprost was approved for use in the U.S. on February 10, 2012. Tafluprost, preserved and preservative-free formulations, received marketing approval for the reduction of elevated intraocular pressure (IOP) in open-angle glaucoma and ocular hypertension in several European and Nordic countries as well as Japan, and some other Asia Pacific markets.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Prostanoid FP receptor 21 Target ID: CHEMBL1987 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/202514s003s004lbl.pdf	Agonist 2678		0.5 nM [IC50]
Prostanoid FP receptor 21 Target ID: CHEMBL1987 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15037111	Agonist 2678		0.4 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Unknown 2578
Glaucoma 57 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/202514s003s004lbl.pdf	Secondary	Approved 8429	ZIOPTAN Approved Use Indicated for reducing elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. Launch Date 2012
Ocular hypertension 50 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/202514s003s004lbl.pdf	Secondary	Approved 8429	ZIOPTAN Approved Use Is indicated for reducing elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. Launch Date 2012

C_max

Value	Dose	Co-administered	Analyte	Population
24.4 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18752509	1 drop single, topical dose: 1 drop route of administration: Topical experiment type: SINGLE co-administered:		TAFLUPROST ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
26 pg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202514s000lbl.pdf	1 drop single, topical dose: 1 drop route of administration: Topical experiment type: SINGLE co-administered:		TAFLUPROST ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
405.9 pg × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18752509	1 drop single, topical dose: 1 drop route of administration: Topical experiment type: SINGLE co-administered:		TAFLUPROST ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
394 pg × min/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202514s000lbl.pdf	1 drop single, topical dose: 1 drop route of administration: Topical experiment type: SINGLE co-administered:		TAFLUPROST ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
0.0015 % 1 times / day multiple, ophthalmic Recommended Dose: 0.0015 %, 1 times / day Route: ophthalmic Route: multiple Dose: 0.0015 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202514Orig1s000MedR.pdf Page: p.66	unhealthy, 27-72 years n = 18 Health Status: unhealthy Condition: open-angle glaucoma \| ocular hypertension Age Group: 27-72 years Sex: M+F Population Size: 18 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202514Orig1s000MedR.pdf Page: p.66	Disc. AE: Eye irritation, Abnormal sensation in eye... AEs leading to discontinuation/dose reduction: Eye irritation (3 patients) Abnormal sensation in eye (1 patient) Lacrimation increased (1 patient) Eye pruritus (3 patients) Blepharitis (1 patient) Intraocular pressure increased (2 patients) Pulmonary fibrosis (1 patient) Scleritis (1 patient) Dry skin (1 patient) Conjunctival disorder (2 patients) Ocular hyperemia (2 patients) Headache (2 patients) Hypertrichosis (1 patient) Cough (1 patient) Eye pain (2 patients) Vision blurred (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202514Orig1s000MedR.pdf Page: p.66
0.0003 % 1 times / day multiple, ophthalmic Dose: 0.0003 %, 1 times / day Route: ophthalmic Route: multiple Dose: 0.0003 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202514Orig1s000MedR.pdf Page: p.66	unhealthy, 60 years n = 1 Health Status: unhealthy Age Group: 60 years Sex: M Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202514Orig1s000MedR.pdf Page: p.66	Disc. AE: Blood pressure increased... AEs leading to discontinuation/dose reduction: Blood pressure increased (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202514Orig1s000MedR.pdf Page: p.66

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
			inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP 270

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 270	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202514Orig1s000ClinPharmR.pdf#page=12 Page: 12.0	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202514Orig1s000PharmR.pdf#page=29 Page: 29.0		AFP-172 2

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:66899	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:66899
ChemicalBook	CB3401660	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB3401660
MolPort	MolPort-020-006-049	https://www.molport.com/shop/molecule-link/MolPort-020-006-049
ZINC	ZINC000013912394	http://zinc15.docking.org/substances/ZINC000013912394

PubMed

Title	Date	PubMed
Pharmacological characteristics of AFP-168 (tafluprost), a new prostanoid FP receptor agonist, as an ocular hypotensive drug.	2004 Apr	15037111
Disposition and metabolism of a novel prostanoid antiglaucoma medication, tafluprost, following ocular administration to rats.	2009 Aug	19477946
Tafluprost for glaucoma.	2011 Oct	21916788
Tafluprost: a novel prostaglandin analog for treatment of glaucoma.	2011 Sep	21858491

Patents

Sample Use Guides

In Vivo Use Guide

Unknown

Route of Administration: Unknown

In Vitro Use Guide

The affinity for the FP receptor shown by AFP-172 (Ki : 0.4 nm) was 12 times that of PhXA85 ( Ki : 4.7 nm), a carboxylic acid of latanoprost. For the prostanoid FP receptor-binding study, it was used a clonal cell line that stably expresses the recombinant human prostanoid FP receptor. The AFP-172 showed a high afﬁnity for the human prostanoid FP receptor, with an EC50 of 0,53 nM.

Name

Type

Language

Tafluprost

Official Name

English

5-Heptenoic acid, 7-[(1R,2R,3R,5S)-2-[(1E)-3,3-difluoro-4-phenoxy-1-buten-1-yl]-3,5-dihydroxycyclopentyl]-, 1-methylethyl ester, (5Z)-

Systematic Name

English

TAFLUPROST [USAN]

Common Name

English

AFP-168

Code

English

TAFLUPROST [VANDF]

Common Name

English

MK-2452

Code

English

TAFLUPROST [ORANGE BOOK]

Common Name

English

isopropyl (Z)-7-[(1R,2R,3R,5S)-2-[(E)-3,3-difluoro-4-phenoxy-but-1-enyl]-3,5-dihydroxy-cyclopentyl]hept-5-enoate

Systematic Name

English

Tafluprost [WHO-DD]

Common Name

English

TAFLUPROST [JAN]

Common Name

English

TAFLUPROST [MART.]

Common Name

English

TAFLUPROST [INCI]

Common Name

English

tafluprost [INN]

Common Name

English

TAFLUPROST [MI]

Common Name

English

Classification Tree Code System Code

WHO-ATC

S01EE05