FP Receptor
Prostanoid FP receptor (prostaglandin F2α receptor), a G protein-coupled receptor. Latanoprost acid shows 2000-fold selectivity towards the FP receptor over the EP3 receptor. It is a selective prostanoid receptor (FP) agonist that specifically activates the FP-PG receptor. The compound also exhibits affinity for EP1 and EP3 receptors but with significantly lower selectivity compared to FP.

Latanoprost acid (10–20 μM; 24 hours) decreases c-fos and NFATc1 protein expression [1]. Latanoprost acid (10μM) strongly inhibits ERK, p38, AKT, and JNK[1]. It also contains 50ng/ml of RANKL. The production of mature osteoclasts is greatly inhibited by latanoprost acid (10 μM, 20 μM) [1].
Latanoprost acid is a selective FP receptor agonist that activates the FP-PG receptor, leading to increased outflow of aqueous humor and reduction of intraocular pressure. Activation of the FP receptor in the ciliary body and trabecular meshwork triggers signaling pathways including the p38 cascade, followed by the c-fos/NFATc1 pathway. This results in increased uveoscleral outflow, the primary mechanism by which latanoprost reduces IOP. Latanoprost acid shows 2000-fold selectivity towards the FP receptor over the EP3 receptor.

At a dosage of 20 mg/kg, latanoprost acid (intraperitoneal injection; 20 mg/kg; once daily for 7 days) effectively inhibits LPS-induced bone degradation [1].
In vivo, latanoprost acid (formed from the isopropyl ester prodrug latanoprost) reduces intraocular pressure by increasing the outflow of aqueous humor through the uveoscleral pathway. Latanoprost is a prostanoid selective FP receptor agonist that is believed to reduce IOP by increasing the outflow of aqueous humor. Latanoprost ophthalmic solution is indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. The compound was the first prostaglandin analogue available for the treatment of glaucoma and is well documented.

In vitro receptor binding assays for latanoprost acid involve measuring the compound's affinity for the FP receptor using radioligand displacement techniques. Membranes from cells expressing human FP receptors are incubated with a radiolabeled FP ligand (such as 3H-PGF2α) and increasing concentrations of latanoprost acid. Bound and free ligand are separated by filtration, and radioactivity is measured by scintillation counting. The compound shows 2000-fold selectivity towards the FP receptor over the EP3 receptor.

Western Blot Analysis[1]
Cell Types: Bone marrow-derived macrophages (BMM)
Tested Concentrations: 10 μM, 20 μM
Incubation Duration: 24 hrs (hours)
Experimental Results: The he protein expression of c-fos and NFATc1 was diminished.
Cellular assays for latanoprost acid involve measuring the compound's effects on FP receptor-mediated signaling in cells expressing the FP receptor. Cells are treated with various concentrations of latanoprost acid, and downstream signaling events such as calcium mobilization, MAP kinase activation, or changes in gene expression are measured. These assays confirm that latanoprost acid is a selective FP receptor agonist that activates the FP-PG receptor.

Animal/Disease Models: 8weeks old C57BL/6J mice [1]
Doses: 20 mg/kg
Route of Administration: intraperitoneal (ip) injection; one time/day for 7 days
Experimental Results: 20 mg/kg dose can Dramatically prevent bone destruction caused by LPS.
In vivo animal studies for latanoprost acid typically involve ocular administration (topical eye drops) to animal models of glaucoma or ocular hypertension, such as normotensive or hypertensive rabbits, dogs, or monkeys. Intraocular pressure is measured using tonometry before and after treatment. The compound's ability to reduce IOP is assessed over time. These studies establish the efficacy and dose-response relationship of latanoprost acid in reducing intraocular pressure. The prodrug latanoprost is typically used in these studies due to its better corneal penetration.

Pharmacokinetic studies of latanoprost acid focus on its ocular pharmacokinetics following topical administration of the isopropyl ester prodrug latanoprost. The prodrug is hydrolyzed to the active free acid (latanoprost acid) upon corneal penetration. Latanoprost acid shows 2000-fold selectivity towards the FP receptor over the EP3 receptor. The compound's clinical application is limited by its poor solubility and fast clearance rate. Following topical administration, latanoprost acid reaches the site of action in the eye and is cleared from the systemic circulation rapidly, minimizing systemic side effects.

Preclinical toxicity studies of latanoprost acid have demonstrated a favorable safety profile for ophthalmic use. Unlike PGF2α or other naturally occurring prostanoids, latanoprost acid causes very little ocular irritation or hyperemia. This is likely due to the fact that PGF2α analogues like latanoprost acid are as potent as the parent compound but show increased receptor selectivity. The compound's selectivity for the FP receptor over other prostanoid receptors contributes to its favorable tolerability profile.

[1]. Effects of prostaglandins on the aqueous humor outflow pathways. Surv Ophthalmol. 2002 Aug;47 Suppl 1:S53-64.

[2]. The prevention of latanoprost on osteoclastgenesis in vitro and lipopolysaccharide-induced murine calvaria osteolysis in vivo. J Cell Biochem. 2018 Jun;119(6):4680-4691.

Latanoprost free acid is a prostaglandin Fα analogue, in which the pentyl group is replaced by a 2-phenylethyl group and the 13,14-double bond is formally hydrogenated. Its isopropyl ester prodrug, latanoprost, is used to treat open-angle glaucoma and ocular hypertension. It has anti-glaucoma, antihypertensive, and EC 4.2.1.1 (carbonic anhydrase) inhibitory effects. It is a prostaglandin Fα and a hydroxymonocarboxylic acid. Certain prostaglandins (PGs), including FP receptor agonists, can reduce intraocular pressure by increasing uveal-scleral outflow. Although the exact mechanism of increased uveal-scleral outflow is unclear, activation of molecular signaling cascades and increased biosynthesis of certain metalloproteinases appear to be involved. This leads to a reduction in extracellular matrix components within the ciliary muscle, iris root, and sclera. A reduction in extracellular matrix in certain regions of the uveal-scleral pathway may contribute to the mechanism of increased uveal-scleral outflow. Other mechanisms that may promote proteoglycan-mediated increased uveal-scleral outflow include ciliary muscle relaxation, changes in cell morphology, changes in the cytoskeleton, or densification of the extracellular matrix within the uveal-scleral outflow pathway tissue. Future research should elucidate the importance of these different responses that may lead to increased uveal-scleral outflow. There is currently no conclusive evidence that these compounds significantly promote trabecular meshwork outflow. [1]

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Identifying drugs that inhibit osteoclast formation and function is crucial for the treatment of osteolytic diseases characterized by excessive osteoclast formation and bone resorption. Latanoprost (LTP) is an analog of prostaglandin F2α, a drug used to lower intraocular pressure. Prostaglandin F2α has been reported to regulate bone metabolism, but the effect of LTP on osteoclast formation is unclear. This study found that LTP inhibited RANKL-induced osteoclast formation in a dose-dependent manner, which was confirmed by TRAP activity and TRAP staining. In addition, LTP treatment also reduced osteoclast function, manifested as a reduction in the area of osteoclast resorption lacunae. In addition, LTP inhibited the mRNA expression of osteoclast marker genes such as TRAP and cathepsin K. To elucidate the molecular mechanism, we examined the changes in NFATc1 and c-fos mRNA and protein levels after LTP treatment, as well as the phosphorylation of ERK, AKT, JNK and p38. The results showed that LTP inhibited RANKL-induced osteoclast formation and function by inhibiting the ERK, AKT, JNK and p38 signaling pathways, and thus the c-fos/NFATc1 pathway. Consistent with the results of in vitro experiments, we found that LTP administration reversed lipopolysaccharide-induced bone loss using a mouse cranial osteolysis model. In summary, these data suggest that LTP reduces bone loss in lipopolysaccharide-induced mouse cranial osteolysis by inhibiting osteoclast formation and function. Therefore, our study provides evidence that LTP is a potential treatment option for osteolytic bone disease. [2]
Latanoprost acid is the active metabolite of latanoprost, a widely prescribed prostaglandin F2α analogue for the treatment of open-angle glaucoma and ocular hypertension. Latanoprost was the first prostaglandin analogue available for the treatment of glaucoma and is well documented. Today, prostaglandins contribute significantly to the success of glaucoma drug therapy. Latanoprost acid shows 2000-fold selectivity towards the FP receptor over the EP3 receptor. Its clinical application is limited by its poor solubility and fast clearance rate, which is why the isopropyl ester prodrug is used clinically.

C23H34O5

390.52

390.24

C, 70.74; H, 8.78; O, 20.48

41639-83-2

130209-82-4; (ethanol solution); 41639-83-2 (acid);

6441636

Colorless to light yellow liquids

1.2±0.1 g/cm3

609.1±50.0 °C at 760 mmHg

336.2±26.6 °C

0.0±1.8 mmHg at 25°C

1.564

2.22

4

5

12

28

472

5

C(=C/C[C@@H]1[C@@H](CC[C@H](CCC2=CC=CC=C2)O)[C@@H](C[C@@H]1O)O)/CCCC(=O)O

HNPFPERDNWXAGS-NFVOFSAMSA-N

InChI=1S/C23H34O5/c24-18(13-12-17-8-4-3-5-9-17)14-15-20-19(21(25)16-22(20)26)10-6-1-2-7-11-23(27)28/h1,3-6,8-9,18-22,24-26H,2,7,10-16H2,(H,27,28)/b6-1-/t18-,19+,20+,21-,22+/m0/s1

(Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(3R)-3-hydroxy-5-phenylpentyl]cyclopentyl]hept-5-enoic acid

PhXA-85; PhXA85; 17-phenyl-13,14-dihydro trinor Prostaglandin F2α; Lat-FA; Latanoprost acid; Phxa 85; Phxa-85; CHEBI:63925; latanoprost free acid; Latanoprostacid; Latanprost Free Acid;

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)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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