Latanoprost (free acid)
(Synonyms: 拉坦前列腺素(游离酸)) 目录号 : GC41229
Potent FP receptor agonist
Cas No.:41639-83-2
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
Latanoprost is an F-series prostaglandin (PG) analog which has been approved for use as an ocular hypotensive drug. Latanoprost is an isopropyl ester, a prodrug form which is converted to latanoprost (free acid) by endogenous esterase enzymes. The free acid form is 200 times more potent than latanoprost as an FP receptor ligand for the human recombinant FP receptor. Latanoprost is the isopropyl ester of a PGF2α analog containing an aromatic group (17-phenyl) in the ω-chain. Lat-FA is the corresponding carboxylic acid of this analog. Lat-FA is a potent FP receptor agonist with an EC50 of 3.6 nM for human FP receptors, which is twice the potency of PGF2α. The efficacy of PG analog esters for the treatment of glaucoma correlates closely with the FP receptor binding affinity of the free acid. However, Lat-FA is more irritating and less effective than the prodrug latanoprost when applied directly to the eyes of human glaucoma patients.
| Cas No. | 41639-83-2 | SDF | |
| 别名 | 拉坦前列腺素(游离酸) | ||
| Canonical SMILES | O[C@@H]1[C@H](C/C=C\CCCC(O)=O)[C@@H](CC[C@@H](O)CCC2=CC=CC=C2)[C@H](O)C1 | ||
| 分子式 | C23H34O5 | 分子量 | 390.5 |
| 溶解度 | DMF: >100 mg/ml (from Fluprostenol),DMSO: >100 mg/ml (from Fluprostenol),Ethanol: >100 mg/ml (from Fluprostenol),PBS pH 7.2: >0.8 mg/ml (from 17-phenyl tri | 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 | 2.5608 mL | 12.8041 mL | 25.6082 mL |
| 5 mM | 0.5122 mL | 2.5608 mL | 5.1216 mL |
| 10 mM | 0.2561 mL | 1.2804 mL | 2.5608 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。
The mechanisms by which Latanoprost free acid inhibits human carbonic anhydrase I and II
Biol Pharm Bull 2008 May;31(5):796-801.PMID:18451496DOI:10.1248/bpb.31.796.
Latanoprost, a prostaglandin F2 alpha analogue, has been shown to be an effective ocular hypotensive agent when used alone on ocular hypertensive or open angle glaucoma patients. Carbonic anhydrase (CA) inhibitors are also used to reduce ocular hypertension by decreasing aqueous humor secretion, and are given in combination with prostaglandin F2 alpha analogue. It has been shown that prostaglandin F2 alpha, Minprostin F2 alpha, has been shown to increase the carbonic anhydrase (CA) activity and blood pressure. However, the effects of Latanoprost on CA have not been clarified. Therefore, we studied the effects of Latanoprost free acid on human carbonic anhydrase (HCA) I and II using the stopped flow method. Latanoprost free acid inhibited the hydration activity of HCA I or II by a noncompetitive mechanism. The inhibition constants (Ki) of Latanoprost free acid for HCA I and II were 0.22 and 2.3 mM, respectively. Therefore, Latanoprost free acid is a weak inhibitor of HCA I or II. AutoDock simulation of the Latanoprost free acid-HCA I or II complex showed that the carboxylic moiety of Latanoprost free acid, which is located at the end of the molecule, binds to the zinc ion of the active site by stretching of the chain of Latanoprost free acid through the narrow and deep active site cavity of HCA I or II. In the active site cavity of HCA I or II, one side is hydrophilic and the other is hydrophobic. AutoDock simulation results clearly showed that Latanoprost free acids lie down on the hydrophobic sides of the active site cavities in HCA I and II. The noncompetitive inhibition mechanism and the binding mode of Latanoprost free acid indicate that the behavior of Latanoprost free acid is very similar to that of simple anions.
A comparative study of a preservative-free Latanoprost cationic emulsion (Catioprost) and a BAK-preserved Latanoprost solution in animal models
J Ocul Pharmacol Ther 2012 Oct;28(5):515-23.PMID:22671995DOI:10.1089/jop.2011.0245.
Purpose: Benzalkonium chloride (BAK), a common preservative in eye drops, can induce ocular surface toxicity that may decrease glaucoma therapy compliance. The ocular hypotensive effect, pharmacokinetic (PK) profiles, and local tolerance of a preservative-free Latanoprost 0.005% cationic emulsion (Catioprost(®)), and a BAK-preserved Latanoprost 0.005% solution (Xalatan(®)), were compared. Methods: The ocular hypotensive effect was evaluated in monkeys with elevated intraocular pressure (IOP) induced by laser photocoagulation of the trabecular meshwork. Each monkey (n=8) received both Latanoprost formulations once daily for 5 consecutive treatment days in a crossover design with at least a 2-week washout period between treatments. IOP was measured at baseline (on day 1, no instillation), on vehicle treatment day (day 0), and on treatment days 1, 3, and 5 before drug instillation and then hourly for 6 h. In rabbits, the ocular and systemic concentrations of Latanoprost free acid were determined following a single instillation and the local tolerance of twice daily instillations over 28 days was assessed. Results: Both the preservative-free and BAK-preserved Latanoprost formulations shared the same efficacy profile with the maximum IOP reduction occurring 2 h after each morning dose (-15%, -20%, and -26%; -15%, -23%, and -23% on days 1, 3, and 5, respectively) and lasting through 24 h. The equivalence in efficacy was confirmed by the PK data demonstrating similar area under the curves (AUCs). While both formulations were well tolerated, the incidence of conjunctival hyperemia was reduced by 42% with the BAK-free Latanoprost cationic emulsion. Conclusions: In animal models, a preservative-free Latanoprost cationic emulsion was as effective as Xalatan(®) for lowering IOP with an improved ocular tolerance profile.
Development and validation of a liquid chromatography/electrospray ionization tandem mass spectrometry method for the quantification of Latanoprost free acid in rabbit aqueous humor and ciliary body
J Mass Spectrom 2011 Nov;46(11):1168-74.PMID:22124989DOI:10.1002/jms.2004.
A rapid, selective and sensitive method for quantification of Latanoprost free acid in rabbit aqueous humor (AH) and ciliary body (CB) using reverse phase-high performance liquid chromatography coupled with electrospray ionization (ESI)-mass spectrometry/mass spectrometry has been developed and validated. Quantification in AH and CB was achieved by stable isotope dilution employing tetra-deuterated analog of Latanoprost free acid, used as internal standard. Sample preparation was based on protein precipitation with methanol in AH, and on liquid extraction with a mixture of ethyl acetate and isopropanol 60:40 (v/v) in CB. Elution was achieved on an octylsilica (C8) column, using an isocratic elution method. Detection was performed on a triple quadrupole mass spectrometer, using ESI in positive ion selected reaction monitoring mode. Calibration curves were linear in the validated concentration ranges of 10-160 ng/mL in AH and 80-1280 ng/g in CB. The accuracy and precision values, obtained from three different sets of quality control samples, each analyzed in triplicate on three different days, were within the generally accepted criteria for analytical methods (< 15%). The limit of detection was 30.66 pg/mL in AH and 237.75 pg/g in CB. The assay proved to be accurate and precise when applied to the in vivo study of Latanoprost free acid in rabbit AH and CB after single administration of an eye drops containing Latanoprost.
A Comparative Ocular Pharmacokinetics Study of Preservative-Free Latanoprost Unit-Dose Eye Drops and a Benzalkonium Chloride-Preserved Branded Product Following Topical Application to Rabbits
J Ocul Pharmacol Ther 2020 Sep;36(7):522-528.PMID:32310714DOI:10.1089/jop.2019.0102.
Purpose: To evaluate the aqueous humor pharmacokinetics of a preservative-free 0.005% Latanoprost unit-dose eye drop (test drug) compared with that of a benzalkonium chloride (BAK)-preserved 0.005% Latanoprost branded product (control drug) following topical application to rabbits. Methods: A total of 120 healthy New Zealand albino rabbits were administrated test eye drops (T group) or control eye drops (C group) for a comparative pharmacokinetics study. The aqueous humor was collected at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 h after a single dose or multiple doses. Ultraperformance liquid chromatography-tandem quadrupole mass spectrometry was employed to detect Latanoprost free acid (LTA, the active metabolite of Latanoprost) in the aqueous humor. Results: For the single-dose study, there was no significant difference (t-test, P > 0.05) in the peak concentration (Cmax) of LTA in aqueous humor between the T group (69.0 ± 23.4 ng/mL) and C group (73.8 ± 28.7 ng/mL). The area under the curve values over 12 h (AUC0-12h) of LTA for the 2 groups were 254.4 (ng/mL) × h and 219.5 (ng/mL) × h, respectively. For the multidose study, there was also no significant difference (t-test, P > 0.05) in the Cmax of LTA in the aqueous humor between the T group (86.8 ± 21.2 ng/mL) and C group (70.5 ± 25.9 ng/mL). The AUC0-12h values of LTA for the 2 groups were 274.5 (ng/mL) × h and 256.3 (ng/mL) × h, respectively. Conclusions: The preservative-free 0.005% Latanoprost unit-dose eye drops demonstrated similar pharmacokinetic properties to the BAK-preserved branded product following topical application to rabbits.
0.005% Preservative-Free Latanoprost Induces Dry Eye-Like Ocular Surface Damage via Promotion of Inflammation in Mice
Invest Ophthalmol Vis Sci 2018 Jul 2;59(8):3375-3384.PMID:30025085DOI:10.1167/iovs.18-24013.
Purpose: To investigate the side effects of preservative-free 0.005% Latanoprost on the murine ocular surface. Methods: We applied 0.005% Latanoprost or vehicle in mice in two patterns for 14 to 28 days. Tear production was measured by phenol red cotton test, and corneal epithelial barrier function was assessed by Oregon-green-dextran (OGD) staining. Periodic acid-Schiff (PAS) staining was used to quantify conjunctival goblet cells (GCs). The expression of matrix metalloproteinase (MMP)-3 and -9, occludin-1 and zonula occludens (ZO)-1 in corneal epithelium was assessed by immunofluorescent staining and/or quantitative real-time PCR (qRT-PCR). Inflammation in conjunctiva was assessed by activation of P38 and NF-κB, infiltration of CD4+ T cells, and production inflammatory cytokines including TNF-α, IL-1β, IFN-γ, IL-17A, and IL-13. Apoptosis in ocular surface was assessed by TUNEL and immunofluorescent staining for activated caspase-3 and -8. Cell viability assay was performed in human corneal epithelial cells. Results: Topical Latanoprost treatment decreased tear production, induced conjunctival GC loss, disrupted the corneal epithelial barrier, and promoted cell apoptosis in the ocular surface. Topical Latanoprost treatment increased the expression of MMP-3 and -9, and decreased the expression of ZO-1 and occludin-1 in the corneal epithelium. Topical application of Latanoprost promoted activation of P38-NF-κB signaling and production of TNF-α and IL-1β in conjunctiva. Topical application of Latanoprost increased CD4+ T cells infiltration, with increased production of IFN-γ and IL-17A and decreased production of IL-13 in conjunctiva. Conclusion: 0.005% Latanoprost induced dry eye-like ocular surface damage via promotion of inflammation in mice.