Fluorometholone binds to the glucocorticoid receptor with high affinity (IC50 = 1.5 nM; Kd = 2.8 nM in radioligand binding assay). Upon binding, it activates glucocorticoid receptor-mediated gene expression. This leads to the induction of anti-inflammatory proteins and inhibition of inflammatory mediators.

Fluorometholone (25-100 nM; 12 hours, 24 hours) activates glucocorticoid receptors in conjunctival and corneal epithelial cells, increasing the expression of the MUC1, MUC4, MUC16, and MUC19 genes [1].
In vitro studies show that fluorometholone (25-100 nM, 12-24 hours) increases the gene expression of MUC1, MUC4, MUC16, and MUC19 in ocular surface cells. The compound’s anti-inflammatory effects are mediated through glucocorticoid receptor activation and subsequent modulation of gene transcription.

Fluorometholone exhibits anti-inflammatory and anti-allergic activity in vivo when applied topically to the eye. It inhibits edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, deposition of collagen, and scar formation associated with inflammation.

For non-cellular receptor binding assays, fluorometholone’s affinity for the glucocorticoid receptor can be evaluated using radioligand binding studies. Glucocorticoid receptor-containing preparations are incubated with radiolabeled dexamethasone or other glucocorticoid ligands and varying concentrations of fluorometholone. Binding displacement curves are generated to determine IC50 and Kd values.

In vitro cellular assays for fluorometholone involve treating glucocorticoid receptor-positive cell lines (e.g., ocular surface cells) with the compound and measuring receptor-mediated transcriptional activity. Reporter gene assays using glucocorticoid response element (GRE)-luciferase constructs are commonly used. Gene expression changes are quantified by qPCR to assess the induction of anti-inflammatory genes.

In vivo animal experiments for fluorometholone involve topical ocular administration to animal models of ocular inflammation. Efficacy is assessed by measuring inflammatory parameters such as cell infiltration, protein extravasation, and clinical signs of inflammation. The compound’s effects on corneal wound healing and intraocular pressure may also be evaluated in appropriate models.

Fluorometholone is a lipophilic steroid with a molecular weight of 376.47. After topical ocular administration, it penetrates the cornea and reaches the anterior segment of the eye. Systemic absorption is minimal due to the topical route of administration, limiting systemic side effects. The compound is metabolized in the eye and systemically.

Use of the medication during pregnancy and lactation ◉ Overview of use during lactation
There is currently no information regarding the use of fluorometholone eye drops during lactation. Due to limited absorption by the eye, fluorometholone eye drops are not expected to have any adverse effects on breastfed infants. After using the eye drops, to significantly reduce the amount of medication entering breast milk, press the tear duct at the corner of the eye for at least 1 minute, then blot away any excess medication with absorbent paper.
◉ Effects on breastfed infants
As of the revision date, no relevant published information was found.
◉ Effects on breastfeeding and breast milk
As of the revision date, no relevant published information was found.
Ocular corticosteroids such as fluorometholone can increase intraocular pressure, delay wound healing, and increase the risk of cataract formation and secondary infections with prolonged use. They inhibit the inflammatory response to various inciting agents and probably delay or slow healing. Systemic side effects are minimal with topical use.

[1]. Fluorometholone Modulates Gene Expression of Ocular Surface Mucins. Acta Ophthalmol. 2019 Dec;97(8):e1082-e1088.

Fluorometholone belongs to the class of glucocorticoids. Its structure is δ(1)-progesterone, with hydroxyl groups at positions 11β and 17, a methyl group at position 6α, and a fluorine group at position 9. It is used to treat inflammation of the palpebral conjunctiva, bulbar conjunctiva, cornea, and anterior segment of the eye that is sensitive to corticosteroids. It is an anti-inflammatory drug. Fluorometholone is a fluorinated steroid, 11β-hydroxy steroid, 20-oxo steroid, 3-oxo-δ(1),δ(4)-steroid, glucocorticoid, 17α-hydroxy steroid, and tertiary α-hydroxy ketone. It is functionally related to δ(1)-progesterone. It is a glucocorticoid, usually used as eye drops to treat allergic and inflammatory diseases of the eye. It has also been used topically to treat various skin diseases. (Excerpt from Martindale Pharmacopoeia, 30th edition, p. 732) Fluorometholone is a corticosteroid. The mechanism of action of fluorometholone is as a corticosteroid hormone receptor agonist. Fluorometholone is a synthetic glucocorticoid with anti-inflammatory and anti-allergic properties. Fluorometholone exerts its effects by interacting with cytoplasmic glucocorticoid receptors, subsequently activating glucocorticoid receptor-mediated gene expression. It induces the synthesis of certain anti-inflammatory proteins while inhibiting the synthesis of certain inflammatory mediators. Therefore, chronic inflammation and autoimmune responses are generally reduced. A glucocorticoid, commonly used as eye drops to treat allergic and inflammatory eye conditions. It has also been used topically to treat various skin conditions. (From Martindale Pharmacopoeia, 30th edition, p. 732) See also: Fluorometholone acetate (active ingredient); Fluorometholone; Sodium sulfacetamide (ingredient).

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Indications
For the treatment of inflammation of the palpebral conjunctiva, bulbar conjunctiva, cornea, and anterior segment of the eye in patients sensitive to corticosteroids.
FDA label

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Mechanism of Action
There is currently no universally accepted mechanism of action for ocular corticosteroids. However, the mechanism of action of corticosteroids is believed to be the induction of phospholipase A2-inhibiting proteins (collectively known as lipocortin). These proteins are presumed to control the biosynthesis of potent inflammatory mediators such as prostaglandins and leukotrienes by inhibiting the release of their common precursor, arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2. The primary target of phospholipase A2 is the cytoplasmic glucocorticoid receptor. After receptor-receptor binding, the newly formed receptor-ligand complex translocates to the nucleus and binds to multiple glucocorticoid response elements (GREs) in the promoter regions of target genes. Subsequently, the DNA-bound receptor interacts with basal transcription factors, leading to increased expression of specific target genes.

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Pharmacodynamics
Corticosteroids such as fluorometholone can inhibit inflammatory responses induced by a variety of factors and may delay or slow wound healing. They inhibit inflammation-related edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, collagen deposition, and scar formation.
Fluorometholone is approved for ophthalmic use and is available under various brand names including FML, FML Forte Liquifilm, FML-S, Flarex, and Fluor-OP. It is indicated for the treatment of steroid-responsive inflammatory conditions of the eye. The compound’s efficacy and safety profile make it a commonly prescribed ophthalmic corticosteroid.

C22H29FO4

376.47

376.204

426-13-1

Fluorometholone (Standard);426-13-1

9878

White to off-white solid powder

1.3±0.1 g/cm3

527.1±50.0 °C at 760 mmHg

292 - 303ºC

272.6±30.1 °C

0.0±3.1 mmHg at 25°C

1.574

2.02

2

5

1

27

787

8

C[C@H]1C[C@H]2[C@@H]3CC[C@@]([C@]3(C[C@@H]([C@@]2([C@@]4(C1=CC(=O)C=C4)C)F)O)C)(C(=O)C)O

FAOZLTXFLGPHNG-KNAQIMQKSA-N

InChI=1S/C22H29FO4/c1-12-9-17-15-6-8-21(27,13(2)24)20(15,4)11-18(26)22(17,23)19(3)7-5-14(25)10-16(12)19/h5,7,10,12,15,17-18,26-27H,6,8-9,11H2,1-4H3/t12-,15-,17-,18-,19-,20-,21-,22-/m0/s1

Pregna-1,4-diene-3,20-dione, 9-fluoro-11,17-dihydroxy-6-methyl-, (6alpha,11beta)-

NSC 33001 NSC-33001 NSC33001

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.

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

DMSO : ~50 mg/mL (~132.82 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.64 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 25.0 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.)