FP receptor

曲伏前列素对 DP、EP1、EP3、EP4、IP 和 TP 受体具有亚微摩尔亲和力[1]。

在新西兰白化兔 (NZA) 中，1 μg 剂量的曲伏前列素产生的眼部刺激发生率低于 PGF20 异丙酯。猫局部眼部使用曲伏前列素 0.01、0.03 和 0.1 μg 剂量后可产生显着的缩瞳作用。在高眼压猴中，每日两次施用 0.1 和 0.3 μg 曲伏前列素可使眼压 (IOP) 分别峰值降低 22.7% 和 28.6%。局部应用曲伏前列素在兔子、猫和猴子中具有良好的耐受性，剂量高达 1 μg 时不会引起眼部刺激或不适[1]。

曲伏前列素是一种高亲和力、选择性FP前列腺素全受体激动剂的异丙酯前药。与曲伏前列素酸对FP受体的高亲和力和疗效相反，对DP、EP1、EP3、EP4、IP和TP受体的亲和力仅为亚微摩尔[1]。

评估了多种前列腺素F2α（PGF2α）类似物动员细胞内Ca2+[Ca2+]i和竞争[3H]PGF2α与前列腺素F2α受体（FP）结合的能力。放射性配体结合研究测量了各种FP前列腺素类似物对[3H]PGF 2α的置换，得出了以下亲和力等级：曲伏前列素酸[（+）-16-m-三氟苯氧基四诺PGF 2 a；（+）-氟前列醇]>比马前列素酸（17-苯基三醇或PGF 2 alpha）>>乌诺前列酮（13,14-二氢-15-酮-20-乙基PGF 2阿尔法）=比马前列醇（17-苯三醇或PGE 2α-乙基酰胺）>或=Lumigan（比马前列素眼用溶液）。在FP功能研究中，曲伏前列酸（EC50=17.5-37nM，n=13）、比马前列酸（EC 50=23.3-49.0nM，n=6-12）、乌诺前列酮（EC50=306-1270nm，n=4-8）、比马前列素（EC 50=3070-3940nM，n=4-9）和Lumigan（EC 50=1470-3190nM，n=5-9）通过大鼠（A7r5细胞）、小鼠（3T3细胞）和克隆的人眼部FP前列腺素受体浓度依赖性地刺激[Ca2+]去激活。这些化合物在三种物种的FP受体上的效力等级顺序相似，与确定的结合亲和力非常一致。这些化合物的激动作用被FP受体选择性拮抗剂AL-8810（11β-氟-15-epi-15-茚满基-四硝基-PGF2α）浓度依赖性阻断（Ki=0.6-1.3微M）。这些研究表明，比马前列素、乌诺前列酮和比马前列酸对大鼠、小鼠和人类FP前列腺素受体具有直接激动剂活性，曲伏前列素酸是所测试的合成FP前列腺素类似物中最有效的[2]。

Travoprost produced a lower incidence of ocular irritation than PGF20 isopropyl ester at a dose of 1 microg in the New Zealand albino (NZA) rabbit. Topical ocular application of travoprost produced a marked miotic effect in cats following doses of 0.01, 0.03 and 0.1 microg. In the ocular hypertensive monkey, b.i.d. application of 0.1 and 0.3 microg of travoprost afforded peak reduction in intraocular pressure (IOP) of 22.7% and 28.6%, respectively. Topical application of travoprost was well tolerated in rabbits, cats and monkeys, causing no ocular irritation or discomfort at doses up to 1 microg. Travoprost is a promising ocular hypotensive prostaglandin FP derivative that has the ocular hypotensive efficacy of PGF2alpha isopropyl ester but with less severe ocular side effects.[1]

Absorption, Distribution and Excretion
Following ophthalmic administration, travoprost is absorbed through the cornea. In many patients in multiple-dose pharmacokinetic studies, the plasma concentrations of the free acid were below 0.01 ng/mL, which was the quantitation limit of the assay. In these studies, the mean plasma Cmax of travoprost free acid was 0.018 ± 0.007 ng/mL (ranging from 0.01 to 0.052 ng/mL), and the Tmax was about 30 minutes.
The elimination of travoprost free acid from plasma is rapid. The levels of travoprost free acid were generally below the limit of quantification within one hour after dosing. Less than 2% of the topical ocular dose of travoprost was excreted in the urine within 4 hours as the travoprost free acid.
No information is available.
No information is available.

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Metabolism / Metabolites
Travoprost, an isopropyl ester prodrug, is hydrolyzed by esterases in the cornea to its biologically active free acid. Systemically, travoprost free acid is metabolized to inactive metabolites via beta-oxidation of the α (carboxylic acid) chain to give the 1,2-dinor and 1,2,3,4-tetranor analogs, via oxidation of the 15-hydroxyl moiety, as well as via reduction of the 13, 14 double bond.

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Biological Half-Life
The terminal elimination half-life of travoprost free acid was estimated from fourteen subjects and ranged from 17 minutes to 86 minutes with the mean half-life of 45 minutes.

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
No information is available on the use of travoprost during breastfeeding. Because of its short half-life it is not likely to reach the bloodstream of the infant or cause any adverse effects in breastfed infants. Professional guidelines consider prostaglandin eye drops acceptable during breastfeeding. To substantially diminish the amount of drug that reaches the breastmilk after using eye drops, place pressure over the tear duct by the corner of the eye for 1 minute or more, then remove the excess solution with an absorbent tissue.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
No information is available.

[1]. Preclinical efficacy of travoprost, a potent and selective FP prostaglandin receptor agonist. J Ocul Pharmacol Ther. 2001 Oct;17(5):421-32.

[2]. Real-time intracellular Ca2+ mobilization by travoprost acid, bimatoprost, unoprostone, and other analogs via endogenous mouse, rat, and cloned human FP prostaglandin receptors. J Pharmacol Exp Ther . 2003 Jan;304(1):238-45.

Travoprost is the isopropyl ester of prostaglandin F2alpha in which the pentyl group is replaced by a 3-(trifluoromethyl)phenoxymethyl group. A synthetic analogue of prostaglandin F2alpha, ophthalmic solutions of travoprost are used as a topical medication for controlling the progression of open-angle glaucoma and ocular hypertension, by reducing intraocular pressure. It is a pro-drug; the isopropyl ester group is hydrolysed by esterases in the cornea to the biologically active free acid, fluprostenol. It has a role as an antiglaucoma drug, an antihypertensive agent, a prodrug, an ophthalmology drug and a prostaglandin receptor agonist. It is a prostaglandins Falpha, a member of (trifluoromethyl)benzenes and an isopropyl ester. It is functionally related to a fluprostenol.
Travoprost is a synthetic isopropyl ester prodrug of a prostaglandin F2alpha (F2α) analogue and selective FP prostanoid receptor agonist. It is used to decrease intraocular pressure in open-angle glaucoma and ocular hypertension. Unlike other prostaglandin analogues, travoprost demonstrates full agonism and high selectivity at the prostanoid receptor, reporting a higher efficacy in reducing intraocular pressure and a reduced risk for developing off-target side effects.
Travoprost is a Prostaglandin Analog.
Travoprost is a synthetic lipophilic isopropyl ester prodrug of the active compound travoprost free acid, a prostaglandin F2alpha analog with anti-glaucoma property. Upon administration, travoprost is hydrolysed to a free acid by corneal esterases, and then selectively stimulating the prostaglandin F (FP prostanoid) receptor, thereby increasing the uveoscleral outflow which leads to a reduction in intra-ocular pressure.
A cloprostenol derivative that is used as an ANTIHYPERTENSIVE AGENT in the treatment of OPEN-ANGLE GLAUCOMA and OCULAR HYPERTENSION.

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Drug Indication
Travoprost is indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. It is also used in pediatric patients aged two months to less than 18 years.
Decrease of elevated intraocular pressure in adult patients with ocular hypertension or open-angle glaucoma (see section 5. 1). Decrease of elevated intraocular pressure in paediatric patients aged 2 months to < 18 years with ocular hypertension or paediatric glaucoma (see section 5. 1).
Decrease of elevated intraocular pressure in adult patients with ocular hypertension or open-angle glaucoma (see section 5. 1). Decrease of elevated intraocular pressure in paediatric patients aged 3 years to < 18 years with ocular hypertension or paediatric glaucoma.
Treatment of glaucoma

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Mechanism of Action
Travoprost is a prodrug. Upon administration, travoprost is absorbed through the cornea and hydrolyzed to its active metabolite, travoprost free acid. The ester moiety of the free acid allows for enhanced penetration into the aqueous humour. While the exact mechanism of travoprost is largely unknown, it is believed to be related to its full agonist activity for the prostaglandin FP receptor. By binding to the FP receptor, travoprost free acid increases the outflow of aqueous humour via the trabecular meshwork and uveoscleral pathways, thereby reducing the intraocular pressure.

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Pharmacodynamics
Travoprost demonstrates preferential affinity and full agonist activity for the prostaglandin FP receptor in the nanomolar range. Travoprost shows no significant affinity for other prostanoid or non-prostanoid receptors. Travoprost-induced reduction of intraocular pressure is observed about two hours after administration, and the maximum effect is reached after 12 hours. Significant lowering of intraocular pressure can be maintained for periods exceeding 24 hours with a single dose.

C26H35F3O6

500.5477

500.24

C, 62.39; H, 7.05; F, 11.39; O, 19.18

157283-68-6

5,6-trans-Travoprost; 1563176-59-9

5282226

Colorless to light yellow liquid (Oil like)

1.0±0.1 g/cm3

237.5±9.0 °C at 760 mmHg

90.6±0.0 °C

0.1±0.5 mmHg at 25°C

1.545

3.17

96.22

3

9

13

35

693

5

FC(C1C([H])=C([H])C([H])=C(C=1[H])OC([H])([H])[C@@]([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])O[H])(F)F

MKPLKVHSHYCHOC-AHTXBMBWSA-N

InChI=1S/C26H35F3O6/c1-17(2)35-25(33)11-6-4-3-5-10-21-22(24(32)15-23(21)31)13-12-19(30)16-34-20-9-7-8-18(14-20)26(27,28)29/h3,5,7-9,12-14,17,19,21-24,30-32H,4,6,10-11,15-16H2,1-2H3/b5-3-,13-12+/t19-,21-,22-,23+,24-/m1/s1

propan-2-yl (Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3R)-3-hydroxy-4-[3-(trifluoromethyl)phenoxy]but-1-enyl]cyclopentyl]hept-5-enoate

Fluprostenol isopropyl ester; AL6221; Flu-Ipr; Travatan; Travatan Z; Travoprost; Izba; AL-6221; Travaprost; Otx-tp;

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)

Ethanol: ~60 mg/mL (~119.9 mM)
DMSO: ≥ 41.67 mg/mL (~83.3 mM)

配方 1 中的溶解度: ≥ 2.08 mg/mL (4.16 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 20.8 mg/mL澄清DMSO储备液加入400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.08 mg/mL (4.16 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.08 mg/mL (4.16 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
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7、 以上所有助溶剂都可在 Invivochem.cn网站购买。