Tafluprost (free acid)
(Synonyms: 他氟前列素酸,AFP-172) 目录号 : GC40866
A PGF derivative similar to latanoprost free acid
Cas No.:209860-88-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
A number of 17-phenyl trinor prostaglandin F2α (17-phenyl trinor PGF2α) derivatives have been approved for the treatment of glaucoma. Of these, the ones wherein the 13,14-double bond has been hydrogenated retain relatively good potency, but show a significantly reduced incidence of local irritant side effects. Alternatively, it was recently reported that analogs incorporating a 15-deoxy-15,15-difluoro modification also had a favorable ophthalmic activity profile. Tafluprost is a 2-series, 16-phenoxy analog of PGF2α with the 15,15-difluoro substitution. Tafluprost (free acid) is a very potent FP receptor agonist, with a Ki of 0.4 nM. The ester prodrug forms of tafluprost are also potent ocular hypotensives in monkeys.
| Cas No. | 209860-88-8 | SDF | |
| 别名 | 他氟前列素酸,AFP-172 | ||
| Canonical SMILES | O[C@@H](C[C@@H](O)[C@@H]1/C=C/C(F)(F)COC2=CC=CC=C2)[C@@H]1C/C=C\CCCC(O)=O | ||
| 分子式 | C22H28F2O5 | 分子量 | 410.5 |
| 溶解度 | DMF: 30 mg/ml,DSMO: 30 mg/ml,Ethanol: 30 mg/ml,PBS (pH 7.2): 3 mg/ml | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4361 mL | 12.1803 mL | 24.3605 mL |
| 5 mM | 0.4872 mL | 2.4361 mL | 4.8721 mL |
| 10 mM | 0.2436 mL | 1.218 mL | 2.4361 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Mechanisms of benzalkonium chloride toxicity in a human trabecular meshwork cell line and the protective role of preservative-free Tafluprost
Clin Exp Ophthalmol 2015 Mar;43(2):164-72.PMID:25041649DOI:10.1111/ceo.12390.
Background: Benzalkonium chloride (BAK) is a controversial ophthalmic preservative because of its prominent side-effect profile. In this study, we examined the mechanism of BAK toxicity in human trabecular meshwork cells (HTMC) and compared the effects of BAK with Tafluprost free acid, which is an active form of Tafluprost commercially available in a preservative-free formulation. Methods: Primary HTMC were treated with different BAK concentrations over various exposure times. Cell viability was quantified using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenol tetrazolium bromide assay, and apoptosis was measured by enzyme-linked immunosorbent assay. The cell viability of primary HTMC exposed to various concentrations and times of Tafluprost free acid was also determined. Cells were treated with BAK and Tafluprost free acid for 30 min at 37°C, and cell viability was again assessed. The effect of BAK on the gap junction protein Connexin-43 (Cx43) expression was subsequently examined. Results: BAK treatment resulted in a dose- and time-dependent decline in cell viability. Apoptosis increased following BAK treatment. Tafluprost-free acid treatment did not significantly affect cell viability. Tafluprost co-treatment with BAK resulted in an increase in cell viability as compared with BAK treatment alone. BAK treatment upregulated Cx43 expression in HTMC. Conclusions: These results demonstrate that BAK is harmful to the health of cultured HTMC. Tafluprost is both safe and cytoprotective against BAK for these HTMC. The effect of Tafluprost on the gap junctions of the HTM should be further investigated.
Pharmacokinetics, efficacy and safety profiles of preserved and preservative-free Tafluprost in healthy volunteers
Acta Ophthalmol Suppl (Oxf ) 2008;242:7-13.PMID:18752509DOI:10.1111/j.1755-3768.2008.01380.x.
Purpose: Prostanoid F(2alpha) (PF(2alpha)) analogues are commonly used as first-line treatment of glaucoma. Tafluprost is a newly synthesized PF(2alpha) derivative and represents the first PF(2alpha) analogue with a fully preservative-free formulation. Methods: A randomized, investigator-masked, single-centre, crossover phase I study evaluated the pharmacokinetics, efficacy and safety profiles of preserved and preservative-free Tafluprost 0.0015% eyedrops in healthy volunteers. Both formulations were administered once/day for 8 days each. Plasma concentrations and, consequently, area under the curve (AUC(0-last)), maximum concentration (C(max)) and time to maximum concentration (t(max)) were determined for Tafluprost acid, the biologically active metabolite. Intraocular pressure, adverse events, and ocular and systemic safety parameters were analysed. Results: There were no statistically significant differences in pharmacokinetic parameters between preserved and preservative-free formulations after either single (day 1) or repeated (day 8) dosing. The mean (+/- standard deviation) results for preserved and preservative-free formulations on day 8 were, respectively: AUC(0-last) 581.1 +/- 529.9 pg/min/ml versus 431.9 +/- 457.8 pg/min/ml (p = 0.462); C(max) 31.4 +/- 19.5 pg/ml versus 26.6 +/- 18.0 pg/ml (p = 0.294), and median (range) t(max) 10 (5-15) for both. Generally, plasma concentrations of Tafluprost acid were low at all time-points and were cleared rapidly from the circulatory system. There were no unexpected safety findings. The incidence of ocular hyperaemia was similar in both formulations and was of predominantly moderate severity with preserved Tafluprost and mild severity with preservative-free Tafluprost. Conclusions: Preservative-free Tafluprost appeared to have similar pharmacokinetic properties to the preserved formulation and was generally well tolerated.
Pharmacokinetics, Efficacy, and Safety of the Preservative-free Fixed Combination of Tafluprost 0.0015% and Timolol 0.5% in Healthy Volunteers: A Phase I Comparison vs. the Corresponding Preservative-free Monotherapies
Clin Pharmacokinet 2016 Apr;55(4):485-94.PMID:26391697DOI:10.1007/s40262-015-0331-x.
Purpose: Plasma concentrations of Tafluprost acid and timolol were compared after single (Day 1) and repeated (Day 8) instillations of once-daily Tafluprost 0.0015%-timolol 0.5% preservative-free (PF) fixed-dose combination (FDC), once-daily PF Tafluprost 0.0015%, and twice-daily PF timolol 0.5%. Patients and methods: Fifteen healthy volunteers were randomized to this double-masked, single-center, three-period cross-over study. A wash-out interval of at least 4 weeks separated each three 8-day dosing period. Blood samples were drawn on the first and last day of each dosing period, prior to the morning dose, as well as 5, 10, 15, 30, and 45 min, and 1, 1.5, 2, 4, 8, and 12 h post-dosing. Sample plasma concentrations of Tafluprost acid and/or timolol were determined and maximum concentration (C max), area under the concentration-over-time curve from time zero to the last time point with a quantifiable measurement (AUC0-last), and time to maximum concentration were calculated. Intraocular pressure (IOP), adverse events, and ocular/systemic safety variables were also evaluated. Results: Plasma concentrations of Tafluprost acid were low, with similar levels measured subsequent to either single or repeated dosing of PF FDC and PF Tafluprost. On both sampling days, concentrations peaked at 10 min after the dose, and were cleared from the blood circulation by 30 min; average C max ranged from 17 to 24 pg/mL, and AUC0-last from 3 to 5 pg*h/mL. Plasma concentrations of timolol were comparable after the first dose of PF FDC or PF timolol. Concentrations peaked at 15 min post-dose and diminished in a similar manner after 2 h; average C max was 800 pg/mL and AUC0-last 3900 pg*h/mL. As expected, PF timolol produced a higher Day 8 pre-dose timolol concentration than PF FDC (235 vs. 37 pg/mL; p < 0.001, respectively). The Day 8 post-dose changes in timolol concentrations were relative to this pre-dose difference. All study treatments were well tolerated and safe. PF FDC seemed to provide the best IOP reduction. Conclusions: PF FDC demonstrated good IOP-lowering efficacy and displayed similar pharmacokinetic characteristics to the monotherapy agents. Exposure to timolol was reduced via the halved dosing.
Tafluprost protects rat retinal ganglion cells from apoptosis in vitro and in vivo
Graefes Arch Clin Exp Ophthalmol 2009 Oct;247(10):1353-60.PMID:19551401DOI:10.1007/s00417-009-1122-6.
Background: To investigate whether Tafluprost, which is a prostaglandin-related compound and an anti-glaucoma drug, has a direct anti-apoptotic effect in cultured retinal ganglion cells (RGCs) and rat RGCs in retinas with optic nerve crush (ONC). Methods: RGC-5 cells were induced to undergo apoptosis by a serum deprivation and by exogenous glutamate. The level of cell death with or without Tafluprost was monitored by an XTT assay and by immunocytochemistry with activated caspase-3. Changes in intracellular calcium ([Ca(2+)]i) levels were measured with fluo-4 fluorescence. Rat RGCs were degenerated by ONC. After topical instillation of Tafluprost for 7 and 14 days, the numbers of retrograde-labeled RGCs were counted. Retinal flatmounts were subjected to terminal dUTP nick end labeling (TUNEL) staining to detect apoptotic cells. Results: Tafluprost dose-dependently promoted RGC-5 cell viability with an optimum concentration of 3 microM (p = 0.006). Tafluprost significantly reduced caspase-3-positive cells and suppressed [Ca(+2)]i evoked by exogenous glutamate. The cGMP-dependent protein kinase inhibitor and KT-5823 partially blocked the rescue effect of Tafluprost (p = 0.002). The survival rate of RGCs significantly increased in eyes treated with Tafluprost (p = 0.01), and the prevalence of TUNEL-positive cells was significantly decreased 14 days after ONC (p < 0.001). Conclusions: These data suggest that Tafluprost has an anti-apoptotic effect in RGCs.
Corneal penetration into rabbit aqueous humor is comparable between preserved and preservative-free Tafluprost
Ophthalmic Res 2009;41(2):118-22.PMID:19147999DOI:10.1159/000192082.
Background: Some studies have shown that benzalkonium chloride (BAK), a preservative used in antiglaucoma medications, can increase corneal permeability by acting as a penetration enhancer. Tafluprost is a new prostaglandin F(2)(alpha) analog in clinical use for the treatment of ocular hypertension and glaucoma. Methods: This study evaluated the corneal penetration of preservative-free Tafluprost 0.0015% eye drops and Tafluprost 0.0015% eye drops preserved with 0.01% BAK into the aqueous humor of rabbits. Results: After the administration of a single topical dose (30 microl), the maximum concentrations at 45 min of Tafluprost acid in aqueous humor were 4.50 ng/ml for preservative-free Tafluprost and 3.99 ng/ml for preserved Tafluprost. The area under the concentration-time curves from 45 min to 3 h was 5.14 ng h/ml for the preservative-free formulation and 4.54 ng h/ml for the preserved formulation. Conclusions: These data indicate that BAK does not affect the corneal penetration of Tafluprost into the rabbit aqueous humor.