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Identification
NameTafluprost
Accession NumberDB08819
TypeSmall Molecule
GroupsApproved
DescriptionA prostaglandin analogue ester prodrug used topically (as eye drops) to control the progression of glaucoma and in the management of ocular hypertension. Chemically, tafluprost is a fluorinated analog of prostaglandin F2-alpha. Tafluprost was approved for use in the U.S. on February 10, 2012.
Structure
Thumb
Synonyms
AFP-168
Zioptan
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Saflutansolution4.5 mcgophthalmicMerck Canada IncNot applicableNot applicableCanada
Zioptansolution.0045 mg/.3mLophthalmicMerck Sharp & Dohme Corp.2012-02-10Not applicableUs
Zioptansolution/ drops.0045 mg/.3mLophthalmicAkorn, Inc.2014-11-26Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
TaflotanRegeneron Pharmaceuticals
Brand mixturesNot Available
SaltsNot Available
Categories
UNII1O6WQ6T7G3
CAS number209860-87-7
WeightAverage: 452.5313
Monoisotopic: 452.237430608
Chemical FormulaC25H34F2O5
InChI KeyInChIKey=WSNODXPBBALQOF-VEJSHDCNSA-N
InChI
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
IUPAC Name
propan-2-yl (5Z)-7-[(1R,2R,3R,5S)-2-[(1E)-3,3-difluoro-4-phenoxybut-1-en-1-yl]-3,5-dihydroxycyclopentyl]hept-5-enoate
SMILES
CC(C)OC(=O)CCC\C=C/C[[email protected]]1[C@@H](O)C[C@@H](O)[C@@H]1\C=C\C(F)(F)COC1=CC=CC=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as prostaglandins and related compounds. These are unsaturated carboxylic acids consisting of a 20 carbon skeleton that also contains a five member ring, and are based upon the fatty acid arachidonic acid.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassFatty Acyls
Sub ClassEicosanoids
Direct ParentProstaglandins and related compounds
Alternative Parents
Substituents
  • Prostaglandin skeleton
  • Phenol ether
  • Fatty acid ester
  • Alkyl aryl ether
  • Benzenoid
  • Cyclopentanol
  • Monocyclic benzene moiety
  • Cyclic alcohol
  • Secondary alcohol
  • Carboxylic acid ester
  • Monocarboxylic acid or derivatives
  • Ether
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organofluoride
  • Organohalogen compound
  • Carbonyl group
  • Alkyl halide
  • Alkyl fluoride
  • Alcohol
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Pharmacology
IndicationTafluprost is indicated for reducing elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension.
PharmacodynamicsTafluprost is a novel prostaglandin analog with a high affinity for the fluoroprostaglandin (FP) receptor PGF2α. Tafluprost has an affinity for the FP receptor that is approximately 12 times higher than that of the carboxylic acid of latanoprost, but with almost no potential to bind to other receptors.
Mechanism of actionTafluprost 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.
Related Articles
AbsorptionFollowing instillation, tafluprost is absorbed through the cornea and is hydrolyzed to the biologically active acid metabolite, tafluprost acid. Tafluprost is an ester which makes the drug lipophillic enough to be quickly absorbed through. When administered to the eye, the peak plasma concentration (Cmax) and time to peak plasma concentration (Tmax) of tafluprost acid in healthy subjects was 26 pg/mL and 10 minutes respectively. a AUC, tafluprost acid = 394 pg*min/mL - 432 pg*min/mL.
Volume of distribution

The highest concentration of tafluprost acid was found in the cornea and conjunctiva.

Protein bindingNot Available
Metabolism

Tafluprost is an ester prodrug which is rapidly hydrolyzed by corneal esterases to form its biologically active acid metabolite. Tafluprost acid is further metabolized via fatty acid β-oxidation and phase II conjugation into 1,2,3,4-tetranor acid.

SubstrateEnzymesProduct
Tafluprost
Not Available
Tafluprost free acidDetails
Route of eliminationMean plasma tafluprost acid concentrations were below the limit of quantification of the bioanalytical assay (10 pg/mL) at 30 minutes following topical ocular administration of tafluprost 0.0015% ophthalmic solution. In male rats, it was observed that tafluprost was excreted into the feces.
Half lifeNot Available
ClearanceNot Available
ToxicityMost common ocular adverse reaction is conjunctival hyperemia (range 4% – 20%).
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9644
Blood Brain Barrier+0.8687
Caco-2 permeable+0.5372
P-glycoprotein substrateSubstrate0.5871
P-glycoprotein inhibitor INon-inhibitor0.9015
P-glycoprotein inhibitor IINon-inhibitor0.7888
Renal organic cation transporterNon-inhibitor0.8711
CYP450 2C9 substrateNon-substrate0.8086
CYP450 2D6 substrateNon-substrate0.854
CYP450 3A4 substrateSubstrate0.6508
CYP450 1A2 substrateNon-inhibitor0.75
CYP450 2C9 inhibitorNon-inhibitor0.7344
CYP450 2D6 inhibitorNon-inhibitor0.9056
CYP450 2C19 inhibitorNon-inhibitor0.6873
CYP450 3A4 inhibitorNon-inhibitor0.8038
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7418
Ames testNon AMES toxic0.7286
CarcinogenicityNon-carcinogens0.9028
BiodegradationNot ready biodegradable0.9737
Rat acute toxicity3.7129 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9787
hERG inhibition (predictor II)Non-inhibitor0.7362
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Solutionophthalmic4.5 mcg
Solutionophthalmic.0045 mg/.3mL
Solution/ dropsophthalmic.0045 mg/.3mL
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5886035 No1997-12-182017-12-18Us
Properties
StateLiquid
Experimental Properties
PropertyValueSource
melting point87.5 °CNot Available
boiling point100°C Not Available
water solubilityInsoluble FDA label
logP4.05Not Available
pKa5.5-6.7FDA label
Predicted Properties
PropertyValueSource
Water Solubility0.00528 mg/mLALOGPS
logP4.46ALOGPS
logP4.29ChemAxon
logS-4.9ALOGPS
pKa (Strongest Acidic)14.51ChemAxon
pKa (Strongest Basic)-2.9ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area75.99 Å2ChemAxon
Rotatable Bond Count13ChemAxon
Refractivity120.59 m3·mol-1ChemAxon
Polarizability48.65 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis ReferenceNot Available
General References
  1. Papadia M, Bagnis A, Scotto R, Traverso CE: Tafluprost for glaucoma. Expert Opin Pharmacother. 2011 Oct;12(15):2393-401. doi: 10.1517/14656566.2011.606810. [PubMed:21916788 ]
  2. Pantcheva MB, Seibold LK, Awadallah NS, Kahook MY: Tafluprost: a novel prostaglandin analog for treatment of glaucoma. Adv Ther. 2011 Sep;28(9):707-15. doi: 10.1007/s12325-011-0055-8. Epub 2011 Aug 18. [PubMed:21858491 ]
  3. Takagi Y, Nakajima T, Shimazaki A, Kageyama M, Matsugi T, Matsumura Y, Gabelt BT, Kaufman PL, Hara H: Pharmacological characteristics of AFP-168 (tafluprost), a new prostanoid FP receptor agonist, as an ocular hypotensive drug. Exp Eye Res. 2004 Apr;78(4):767-76. [PubMed:15037111 ]
  4. Fukano Y, Kawazu K: Disposition and metabolism of a novel prostanoid antiglaucoma medication, tafluprost, following ocular administration to rats. Drug Metab Dispos. 2009 Aug;37(8):1622-34. doi: 10.1124/dmd.108.024885. Epub 2009 May 28. [PubMed:19477946 ]
External Links
ATC CodesS01EE05
AHFS Codes
  • 52:40.28
PDB EntriesNot Available
FDA labelDownload (274 KB)
MSDSDownload (22.7 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Prostaglandin f receptor activity
Specific Function:
Receptor for prostaglandin F2-alpha (PGF2-alpha). The activity of this receptor is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system. Initiates luteolysis in the corpus luteum (By similarity). Isoforms 2 to 7 do not bind PGF2-alpha but are proposed to modulate signaling by participating in variant receptor complexes; heterodimers between isoform 1 and ...
Gene Name:
PTGFR
Uniprot ID:
P43088
Molecular Weight:
40054.1 Da
References
  1. Pantcheva MB, Seibold LK, Awadallah NS, Kahook MY: Tafluprost: a novel prostaglandin analog for treatment of glaucoma. Adv Ther. 2011 Sep;28(9):707-15. doi: 10.1007/s12325-011-0055-8. Epub 2011 Aug 18. [PubMed:21858491 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inducer
General Function:
Prostaglandin-endoperoxide synthase activity
Specific Function:
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and brain, and in pathological conditions, such as in cancer. PTGS2 is responsible for production of inflammatory prostaglandins. Up-regulation of PTGS2 is also associated with increased cell adhesion, p...
Gene Name:
PTGS2
Uniprot ID:
P35354
Molecular Weight:
68995.625 Da
References
  1. Roh YJ, Park YG, Kang S, Kim SY, Moon JI: Effects of AFP-172 on COX-2-induced angiogenic activities on human umbilical vein endothelial cells. Graefes Arch Clin Exp Ophthalmol. 2012 Dec;250(12):1765-75. doi: 10.1007/s00417-012-2125-2. Epub 2012 Aug 22. [PubMed:22910791 ]
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Drug created on February 24, 2012 10:29 / Updated on September 27, 2016 02:27