PGF2α
Tafluprost (3 μM, 48 h) causes RGC-5 cells to produce fewer cells[1]. Tafluprost (0.1-100 μM, 48 h) increases RGC-5 cell viability in a dose-dependent way[2].

Tafluprost (3 μM, 48 h) causes RGC-5 cells to produce fewer cells[1]. Tafluprost (0.1-100 μM, 48 h) increases RGC-5 cell viability in a dose-dependent way[2].

Tafluprost (0.0015% AFP168 eye drops, used for 14 days) as a makeup Sprague-Dawley can decrease nerve cell apoptosis, raise RGC cell vitality, and lower intraocular pressure caused by optic nerve compression (ONC)[2].

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In wild-type (WT, C57BL/6) mice, a single topical application of 0.0015% Tafluprost (3 µL) at 18:00 resulted in a significant reduction in intraocular pressure (IOP) measured 3 hours later. The mean IOP reduction was 25.8% (SEM 2.1%) compared to the contralateral untreated eye [3].
In prostaglandin FP receptor-deficient mice (FPKO), Tafluprost (0.0015%) did not significantly lower IOP (mean reduction -0.9%, SEM 1.5%), confirming that its IOP-lowering effect is primarily mediated through the FP receptor [3].
In prostanoid EP3 receptor-deficient mice (EP3KO), the IOP-lowering effect of Tafluprost (0.0015%) was significantly attenuated compared to WT mice (mean reduction 16.5% vs 25.8%). This suggests that part of the drug's effect involves the EP3 receptor pathway [3].
Pretreatment of WT mice with the cyclo-oxygenase inhibitor diclofenac Na (0.1%) 30 minutes before Tafluprost application significantly attenuated the IOP-lowering effect of Tafluprost. However, this attenuating effect of diclofenac was not observed in EP3KO mice. This indicates that endogenous prostaglandins produced via FP receptor activation contribute to the IOP reduction, partly by acting on the EP3 receptor [3].
The IOP-lowering effects of Tafluprost in EP1 and EP2 receptor-deficient mice (EP1KO, EP2KO) were not significantly different from those in WT mice [3].

Cell Line: RGC
Concentration: 0.1, 1, 3, 10, 100 μM
Incubation Time: 48 h
Result: Enhanced the viability of these cells in a dose-dependent fashion, with an optimal concentration of 3μM. Increased the relative fluorescence intensity (RFI).

Male Sprague rat model
0.0015%
Via eye drops

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C57BL/6J, and EP1, EP2, EP3 and postaglandin F (FP) receptor-deficient wild-type (WT), EP1KO, EP2KO, EP3KO and FPKO, respectively mice were bred and acclimatised under a 12-h (6:00-18:00) light-dark cycle. To evaluate effects of tafluprost (0.002%) on IOP at night, a single 3 microl drop of tafluprost solution was applied topically at 18:00 once into one eye in each mouse. IOP was measured 3 h after the application with a microneedle method. To clarify whether endogenous prostaglandin is concerned with the tafluprost-induced IOP reduction, we applied 0.1% diclofenac Na, a cyclo-oxygenase inhibitor or PBS 30 min before the application of tafluprost in WT and EP3KO mice and measured IOP 3 h after the tafluprost application. We also determined whether animals responded predictably to 0.1% bunazosin HCl, a drug known to increase uveoscleral outflow. Results: 3 h after the application of 0.0015% tafluprost, mean (SEM) IOP reductions were 25.8 (2.1)% 26.3 (0.8)% 24.2 (1.4)% 16.5 (1.7)% and -0.9 (1.5)% in WT, EP1KO, EP2KO, EP3KO and FPKO mice, respectively. IOP reductions in EP3KO and FPKO mice were significantly smaller than in WT mice. Pretreatment with diclofenac Na significantly attenuated the IOP lowering effect of tafluprost in WT mice but not in EP3KO mice. Bunazosin HCl lowered IOP significantly in all genotypes by the same amount.[3]

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This clinical study included 28 glaucoma patients (28 eyes) with a treatment history of latanoprost ophthalmic solution (Xalatan(®)) or travoprost ophthalmic solution (Travatan Z(®)), who presented with corneal epithelial disorders. The subjects were switched to BAK-reduced tafluprost, and its effect on the ocular surface was examined after 1 and 2 months of treatment [using fluorescein staining score, hyperemia, tear film breakup time, and intraocular pressure (IOP) lowering]. Results: In all analyzed subjects (N=27), the fluorescein staining score was significantly improved after switching to BAK-reduced tafluprost (P<0.0001). Conversely, the IOP-lowering effect was not notably changed. The subjects switched from latanoprost (n=10) showed significant improvement in fluorescein staining score (P<0.05) as well as in IOP lowering (P<0.01). The subjects switched from travoprost (n=17) also showed significant improvement in fluorescein staining score (P<0.001), but without a significant change in IOP lowering. Conclusions: Tafluprost with reduced BAK has potential as a superior antiglaucoma drug, not only for its IOP-lowering effect, but also for its good corneal safety profile.[4]

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C57BL/6J wild-type mice and genetically engineered prostanoid receptor-deficient mice (EP1KO, EP2KO, EP3KO, FPKO) were used, all aged >8 weeks. Mice were acclimatized under a 12-hour light (06:00-18:00)/12-hour dark cycle.
For IOP-lowering efficacy studies, a 3 µL drop of 0.0015% Tafluprost ophthalmic solution was applied topically to one randomly selected eye of each mouse at 18:00 (onset of dark phase). The contralateral eye served as an untreated control. IOP was measured 3 hours post-application (at 21:00) using a microneedle method under anesthesia (ketamine/xylazine). All procedures during the dark phase were performed under red-light illumination [3].
For the mechanistic study involving cyclo-oxygenase inhibition, a 3 µL drop of either 0.1% diclofenac Na or phosphate-buffered saline (PBS) was applied topically to one eye 30 minutes before the application of Tafluprost (0.0015%, 3 µL) in WT and EP3KO mice. IOP was measured 3 hours after the Tafluprost application [3].
As a control to assess uveoscleral outflow function in different genotypes, a 3 µL drop of 0.1% bunazosin HCl (an α1-adrenergic antagonist known to increase uveoscleral outflow) was applied topically at 18:00, and IOP was measured 3 hours later [3].

Absorption, Distribution and Excretion
Following ophthalmic instillation, tafluprost is absorbed through the cornea and hydrolyzed to its biologically active acidic metabolite, tafluprost acid. Tafluprost is an ester, giving it sufficient lipophilicity for rapid absorption. In healthy subjects, the peak plasma concentration (Cmax) and time to peak concentration (Tmax) after tafluprost acid ophthalmic instillation were 26 pg/mL and 10 minutes, respectively. The AUC of tafluprost acid was 394 pgmin/mL - 432 pgmin/mL. Thirty minutes after topical instillation of 0.0015% tafluprost eye drops, the mean plasma concentration of tafluprost acid was below the limit of quantitation (10 pg/mL) for bioassay. Tafluprost was observed to be excreted in feces in male rats.
Tafluprost acid is found in the highest concentrations in the cornea and conjunctiva.

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Metabolism/Metabolites
Tafluprost is an ester prodrug that can be rapidly hydrolyzed by corneal esterases to produce a biologically active acidic metabolite. Tafluprost acid is further metabolized to 1,2,3,4-tetradecarboxylic acid via fatty acid β-oxidation and II-linked metabolism.

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
There is currently no information regarding the use of tafluprost during lactation. Due to the extremely low plasma concentration after eye drops, it is unlikely to enter breast milk or the infant's bloodstream, and it is unlikely to cause any adverse effects on breastfed infants. Professional guidelines consider the use of prostaglandin eye drops during lactation to be acceptable. To further reduce the amount of medication entering breast milk after using eye drops, press the tear duct at the corner of the eye for at least 1 minute, then wipe away any excess medication with absorbent tissue.
◉ Effects on Breastfed Infants
No relevant published information was found as of the revision date.
◉ Effects on Lactation and Breast Milk
No relevant published information was found as of the revision date.

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In a 3-year clinical study, 10 out of 55 patients (18.2%) reported adverse reactions. Specific adverse events included: pruritus (3 cases), conjunctival hyperemia (3 cases), eyelid pigmentation (2 cases), eye pain (1 case), and deepening of the upper eyelid sulcus (1 case)[5]. One patient (1.8% of the total cohort) discontinued treatment after 18 months due to an adverse reaction (eyelid pigmentation)[5]. During the 3-year study period, 19 patients (34.5%) withdrew from the study for various reasons, including: poor response to intraocular pressure reduction (6 cases), hospitalization (6 cases), cataract surgery (3 cases), relocation (3 cases), and adverse reactions (1 case)[5].

[1]. Prospective observational post-marketing study of tafluprost for glaucoma and ocular hypertension: short-term efficacy and safety. Adv Ther, 2014. 31(4): p. 461-71.

[2]. Tafluprost protects rat retinal ganglion cells from apoptosis in vitro and in vivo. Graefes Arch Clin Exp Ophthalmol. 2009 Oct;247(10):1353-60.

[3]. The IOP-lowering effects and mechanism of action of tafluprost in prostanoid receptor-deficient mice. Br J Ophthalmol. 2007 May;91(5):673-6.

[4]. Comparison of corneal safety and intraocular pressure-lowering effect of tafluprost ophthalmic solution with other prostaglandin ophthalmic solutions. J Ocul Pharmacol Ther, 2014. 30(4): p. 340-5.

[5]. Effects of tafluprost treatment for 3 years in patients with normal-tension glaucoma. Clin Ophthalmol, 2013. 7: p. 1411-6.

Tafluprost is a prostaglandin Fα derivative, a derivative of prostaglandin F2α, in which its carboxylic acid group is converted to the corresponding isopropyl ester, and the 3-hydroxy-1-octenyl side chain is replaced by a 3,3-difluoro-4-phenoxybut-1-enyl group. It is used to treat elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. It is a prostaglandin receptor agonist. It is a prostaglandin Fα derivative, an organofluorine compound, and an isopropyl ester. Its function is related to prostaglandin F2α. Tafluprost is a prostaglandin analog ester prodrug, used topically (in eye drops) to control the progression of glaucoma and treat ocular hypertension. Chemically, tafluprost is a fluorinated analog of prostaglandin F2α. Tafluprost was approved for marketing in the United States on February 10, 2012. Tafluprost is a prostaglandin analog. The mechanism of action of tafluprost is as a prostaglandin receptor agonist. The physiological effects of tafluprost are achieved by increasing prostaglandin activity.

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Drug Indications
Tafluprost is indicated for lowering intraocular pressure in patients with open-angle glaucoma or ocular hypertension.

FDA Label

Treatment of Glaucoma

Mechanism of Action
Tafluprost acid is a selective prostaglandin FP receptor agonist whose mechanism of action is believed to be lowering intraocular pressure (IOP) by increasing aqueous humor outflow. Animal and human studies have shown that its primary mechanism of action is increased uveal-scleral outflow.

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This study aimed to investigate the efficacy and safety of 0.0015% tafluprost eye drops in lowering intraocular pressure (IOP) in real-world clinical application. Methods: We conducted a 2-year prospective observational study, collecting data on intraocular pressure, conjunctival hyperemia score, corneal staining score, and adverse events in glaucoma and ocular hypertension (OH) patients who had not previously received tafluprost treatment at 2, 12, and 24 months. This report analyzes the results at 2 months.
Results: Among 4180 patients from 553 medical institutions in Japan, the majority had primary open-angle glaucoma (POAG, 38.1%) or normal-tension glaucoma (NTG, 44.2%). After 2 months of treatment with tafluprost, intraocular pressure (IOP) decreased significantly by 4.3 ± 5.2 mmHg in patients with POAG, 2.4 ± 2.5 mmHg in patients with NTG, 3.6 ± 5.3 mmHg in patients with POAG, 5.6 ± 7.1 mmHg in patients with other types of glaucoma, and 5.3 ± 4.8 mmHg in patients with high IOP. Intraocular pressure (IOP) decreased significantly by 4.3 ± 4.0 mmHg in patients who had not previously received monotherapy, by 1.9 ± 3.5 mmHg in patients switching from previous treatment regimens, and by 3.7 ± 4.1 mmHg in the combination therapy group. Among patients switching treatment, the primary medication previously used was the prostaglandin analog (PGA) latanoprost (57.4%), followed by travoprost (13.8%). Switching from latanoprost to this product resulted in a significant decrease in IOP, with a mean reduction of 1.5 ± 3.4 mmHg; switching from travoprost resulted in a significant decrease of 1.3 ± 3.7 mmHg. Conjunctival hyperemia scores peaked at 1 month in the treatment-naïve monotherapy and combination therapy groups, while significantly decreased in patients switching from other prostaglandin analogs to this product. No significant changes were observed in corneal staining scores. The incidence of adverse reactions (ADRs) was 7.70% (322/4180 patients), and all major adverse reactions involved the eye or periocular skin. Conclusion: In routine clinical practice, tafluprost showed significant intraocular pressure-lowering effects in patients with various types of glaucoma and high intraocular pressure without any safety issues. Tafluprost was highly effective in any treatment regimen. [1]

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Background: To investigate whether tafluprost (a prostaglandin-related compound and an anti-glaucoma drug) has a direct anti-apoptotic effect on cultured retinal ganglion cells (RGCs) and RGCs in the retina of rats with optic nerve injury (ONC). Methods: Apoptosis of RGC-5 cells was induced by serum deprivation and exogenous glutamate. Cell death levels under tafluprost treatment were monitored by XTT method and activated caspase-3 immunocytochemistry. Changes in intracellular calcium ion concentration ([Ca(2+)]i) were measured by Fluo-4 fluorescence method. Rat retinal ganglion cells (RGCs) degenerate via optic nerve necrosis (ONC). The number of retrogradely labeled RGCs was counted 7 and 14 days after local instillation of tafluprost. Terminal deoxynucleotidyl transferase (TUNEL) staining was performed on retinal plano specimens to detect apoptotic cells. Results: Tafluprost promoted RGC-5 cell survival in a dose-dependent manner, with an optimal concentration of 3 μM (p = 0.006). Tafluprost significantly reduced caspase-3 positive cells and inhibited exogenous glutamate-induced increases in [Ca(+2)]i. cGMP-dependent protein kinase inhibitors and KT-5823 partially blocked the rescue effect of tafluprost (p = 0.002). In eyes treated with tafluprost, RGC survival was significantly improved (p = 0.01), and the proportion of TUNEL-positive cells was significantly reduced 14 days after optic nerve injury (ONC) (p < 0.001). Conclusion: These data suggest that tafluprost has an anti-apoptotic effect on RGCs. [2]

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Tafluprost is a newly synthesized prostaglandin F2α analog developed as an intraocular pressure-lowering drug for the treatment of glaucoma and high intraocular pressure. It is a prodrug ester designed to promote corneal penetration and then hydrolyze to the active carboxylic acid form.[3]
Tafluprost has been reported to have a higher affinity for prostaglandin FP receptors and a stronger intraocular pressure-lowering effect than latanoprost in monkeys and mice.[3]
Tafluprost The main mechanism by which it lowers intraocular pressure is the activation of prostaglandin FP receptors. A secondary component of its action involves the production of endogenous prostaglandins mediated by FP receptors, which then act on prostaglandin EP3 receptors, thereby contributing to the reduction of intraocular pressure.[3]

C25H34F2O5

452.5313

452.237

C, 66.35; H, 7.57; F, 8.40; O, 17.68

209860-87-7

209860-88-8 (Tafluprost acid); 157283-68-6 (Travoprost)

9868491

Colorless to light yellow liquid

1.2±0.1 g/cm3

552.9±50.0 °C at 760 mmHg

288.2±30.1 °C

0.0±1.6 mmHg at 25°C

1.549

4.23

2

7

13

32

614

4

FC(C([H])([H])OC1C([H])=C([H])C([H])=C([H])C=1[H])(/C(/[H])=C(\[H])/[C@@]1([H])[C@@]([H])(C([H])([H])[C@@]([H])([C@]1([H])C([H])([H])C([H])=C([H])C([H])([H])C([H])([H])C([H])([H])C(=O)OC([H])(C([H])([H])[H])C([H])([H])[H])O[H])O[H])F

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

propan-2-yl (Z)-7-[(1R,2R,3R,5S)-2-[(E)-3,3-difluoro-4-phenoxybut-1-enyl]-3,5-dihydroxycyclopentyl]hept-5-enoate

AFP-168; MK2452; AFP-168; MK-2452; Tafluprost; 209860-87-7; Saflutan; 1O6WQ6T7G3; AFP-168; MK 2452; Saflutan; Taflotan; Tapros; Zioptan

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: ≥ 270 mg/mL (~596.7 mM)

Solubility in Formulation 1: ≥ 2.25 mg/mL (4.97 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 22.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.25 mg/mL (4.97 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 22.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.25 mg/mL (4.97 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 22.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)