ocular

Bunazosin Hydrochloride (E 1015) is an alpha(1)-adrenoceptor antagonist used as a systemic antihypertensive and an ocular hypotensive drug.

ot-730 HCl is a novel selective beta blocker prodrug for the study of ocular diseases.

PG-11047 2HCl is an apoptosis-stimulating agent used in the treatment of genitourinary disorders, immune system disorders, genetic disorders and malformations, ocular disorders, and disorders of the blood and lymphatic systems, and in the study of lymphomas and prostate cancer.

Methyl-4-oxoretinoate is a synthetic retinoid compound with anticancer compounds that can induce differentiation and apoptosis in cancer cells.Methyl-4-oxoretinoate is used in the treatment of acne, psoriasis, and other skin disorders.Methyl-4-oxoretinoate has the potential to be used in the treatment of a variety of ocular disorders such as age-related macular degeneration. related macular degeneration).

Diquafosol Tetrasodium is a P2Y2 receptor agonist that stimulates the secretion of mucins from ocular tissues Diquafosol tetrasodium (INS365) improves tear film stability and visual function, as a topical treatment of dry eye disease.

Emedastine (LY188695) is a second generation, selective histamine H1 receptor antagonist with anti-allergic activity. Emedastine reversibly and competitively blocks histamine by binding to H1 receptors, thus blocking its downstream activity. As a result this agent interferes with mediator release from mast cells either by inhibiting calcium ion influx across mast cell/basophil plasma membrane or by inhibiting intracellular calcium ion release within the cells. In addition, emedastine may also inhibit the late-phase allergic reaction mediated through leukotrienes or prostaglandins, or by producing an anti-platelet activating factor effect. Upon ocular administration, emedastine causes a dose-dependent inhibition of histamine-stimulated vascular permeability in the conjunctiva. Emedastine does not affect adrenergic, dopamine, or serotonin receptors.

Latanoprost (Xalatan) is a prostaglandin F2alpha analogue and a prostanoid selective FP receptor agonist with an ocular hypertensive effect.

Brimonidine Tartrate (AGN190342 tartrate) is a quinoxaline derivative and adrenergic α-2 receptor agonist (EC50: 0.45 nM) that is used to manage intraocular pressure associated with open-angle glaucoma or ocular hypertension.

Adenylyl cyclase-IN-1 is a potential adenylyl cyclase inhibitor for ocular hypotonia research [1].

[D-Ala2] Leu-Enkephalinamide, an enkephalin analog, exhibits significant corneal permeability and analgesic properties, making it suitable for ocular disease research [1] [2].

(Rac)-MGV354 (MGV354) is the racemate of MGV354. MGV354 is a soluble activator of guanylate cyclase (sGC)(EC50s of <0.5 nM, and 5 nM in CHO and GTM-3 E cells, respectively).

A number of 17-phenyl trinor prostaglandin F2α (17-phenyl trinor PGF2α) derivatives have been approved for the treatment of glaucoma. Of these, the unsubstituted or meta-substituted aromatic derivatives are the most potent FP receptor agonists. 17-trifluoromethylphenyl trinor PGF2α bears an aromatic ring which is reminiscent of the trifluoromethyl-phenoxy ring of travoprost ((+)-fluprostenol isopropyl ester). As an ocular hypotensive agent, it would be expected that 17-trifluoromethylphenyl trinor PGF2α would act very much like the free acid of travoprost. 17-phenyl trinor PGF2α is a potent luteolytic and abortifacient, with a potency equal to or greater than fluprostenol and cloprostenol.

Bimatoprost is the Allergan trade name for 17-phenyl trinor prostaglandin F2α ethyl amide (17-phenyl trinor PGF2α ethyl amide), an F-series PG analog which has been approved for use as an ocular hypotensive drug. Oxidation of the C-15 hydroxyl group produces 15-keto-17-phenyl trinor PGF2α ethyl amide. 15-keto-17-phenyl trinor PGF2α ethyl amide is a potential metabolite of 17-phenyl trinor PGF2α ethyl amide when 17-phenyl trinor PGF2α ethyl amide is administered to intact animals. No pharmacological studies on 15-keto-17-phenyl trinor PGF2α ethyl amide have been reported.

Homatropine hydrochloride is an orally active anticholinergic agent that induces rapid pupil dilation with cycloplegic effects and possesses antitussive properties. It is utilized in research pertaining to ocular diseases and coughs [1].

Cyclo(RGDyC), a cyclic pentapeptide, exhibits anti-angiogenic properties and has been investigated in conjunction with liposomal delivery systems for the study of ocular neovascular diseases and cancer [1] [2].

N-Desethyl Bimatoprost (17-phenyl trinor PGF2α amide) is an F-series PG analog in which the C-1 carboxyl group has been modified to an unsubstituted amide. PG esters have been shown to have ocular hypotensive activity. PG N-ethyl amides were recently introduced as alternative PG hypotensive prodrugs. Although it has been claimed that PG amides are not converted to the free acids in vivo, studies have shown that bovine and human corneal tissue converts the amides of various PGs to the free acids with a conversion efficiency of about 10-20% relative to the hydrolysis of isopropyl esters. 17-phenyl trinor PGF2α amide would be expected to show the typical intraocular effects of latanoprost, but with the much slower hydrolysis pharmacokinetics of the PG N-amides.

Bimatoprost is an F-series prostaglandin (PG) analog which has been approved for use as an ocular hypotensive drug. Oxidation of the C-15 hydroxyl group and amide hydrolysis of Bimatoprost produces 15-keto-17-phenyl trinor PGF2α. 15-keto-17-phenyl trinor PGF2α is a potential metabolite of bimatoprost when administered to animals. 15-keto PG analogs are potential minor impurities in commercial preparations of their corresponding bulk drug compounds. Although much less potent that the parent compound, 15-keto PGs still retain the ability to produce a small but measurable decrease (1 mm Hg) in the intraocular pressure of normal cynomolgus monkeys when administered at a dose of 1 μg/eye. 15-keto Latanoprost (15-keto-17-phenyl-13,14-dihydro trinor PGF2α isopropyl ester) is a miotic in the normal cat eye, causing an 8 mm reduction in pupillary diameter at 5 μg/eye. Again, this is not as potent as many other F-type PGs; for example, PGF2α will produce this degree of miosis at a dose of less than 1 μg/eye.

Flavanone hydrazine is a potent non-steroidal anti-inflammatory agent that effectively inhibits lens protein-induced ocular inflammation.

A number of 17-phenyl trinor prostaglandin F2α(17-phenyl trinor PGF2α) derivatives have been approved for the treatment of glaucoma.1,2,3Of 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.417-trifluoromethylphenyl-13,14-dihydro trinor PGF2αbears an aromatic ring which is reminiscent of the trifluoromethyl-phenoxy ring of travoprost ((+)-fluprostenol isopropyl ester). As an ocular hypotensive agent, it would be expected that 17-trifluoromethylphenyl-13,14-dihydro trinor PGF2αwould act very much like the free acid of latanoprost.

17-phenyl trinor Prostaglandin F2α (17-phenyl trinor PGF2α) is a metabolically stable analog of PGF2α and is a potent agonist for the FP receptor, binding with a relative potency of 756% compared to that of PGF2α. The ethyl amide of 17-phenyl trinor PGF2α bimatoprost has been approved for use as an ocular hypotensive drug. 17-phenyl trinor PGF2α methyl amide is an analog of bimatoprost. Its biological and toxicological properties have not been evaluated.

Latanoprost is an F-series prostaglandin analog which has been approved for use as an ocular hypotensive drug. 5-trans Latanoprost is an isomer of latanoprost wherein the double bond between carbons 5 and 6 has been changed from cis (Z) to trans (E). The trans isomer of latanoprost occurs as an impurity of between 2-5% in most commercial preparations of the bulk drug product. The present compound was prepared primarily as an analytical standard for detection and quantitation of this impurity. From what can be inferred from the study of other trans isomers of F-type prostaglandins, 5-trans latanoprost's biological activity is likely to be similar to that of the cis isomer. However, there are no specific published reports on the biological activity, and on the intraocular hypotensive activity in particular, of 5-trans latanoprost.

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 a ligand for the human recombinant FP receptor. 5-trans Latanoprost (free acid) is an isomer of latanoprost (free acid) wherein the double bond between carbons 5 and 6 has been changed from cis (Z) to trans (E). The trans isomer of latanoprost occurs as an impurity in commercial preparations of the bulk drug product. The present compound was prepared primarily as an analytical standard for detection and quantitation of this impurity. From what can be inferred from the study of other trans isomers of F-type prostaglandins, the biological activity of this isomer is likely to be similar to that of the cis isomer. However, there are no specific published reports on the biological activity, and on reducing intraocular pressure in particular, of 5-trans latanoprost.

H4R antagonist 3 is a novel histamine-4 receptor (H4R) antagonist with an EC50 <10 mM.H4R antagonist 3 has potential inflammatory activity for the study of autoimmune, allergic and ocular diseases.

(D-Arg1,D-Pro2,D-Trp7,9,L-Leu11)-Substance P (acetate), an antagonist for Substance P and Bombesin, modulates ocular inflammatory responses triggered by antidromic trigeminal nerve stimulation [1].

Interphotoreceptor retinoid-binding protein (651-670) (IRBP651-670), a peptide fragment of retinoid-binding protein 3 (also known as IRBP), plays a crucial role in the visual cycle by facilitating the transport of retinol and retinal between photoreceptor cells and the retinal pigment epithelium. This transport is essential for the regeneration of pigments necessary for vision. When administered at a dose of 300 µg/animal, IRBP651-670 induces autoimmune uveoretinitis in C57BL/6 mice, a model possessing the H-2b haplotype. This immunization leads to increased levels of ocular cytokines including IL-1β, IL-6, IL-17, TNF-α, and IFN-γ, promotes immune cell infiltration into the eye, and results in photoreceptor cell damage.

Thromboxane B3 (TXB3), the stable hydrolysis product of TXA3, is synthesized from eicosapentaenoic acid (EPA) through the action of COX and thromboxane synthase enzymes. This compound is biosynthesized in several tissues, including seminal vesicles, lungs, polymorphonuclear leukocytes (PMNL), and ocular tissues.

Foslevcromakalim (QLS-101), an ATP-sensitive potassium channel opener, serves as a proagent for ocular hypotensive effects [1] [2].

GAT229 is a positive allosteric modulator of cannabinoid receptor 1 (CB1) and the S-(-) enantiomer of the CB1 modulator GAT211. It does not activate the receptor on its own but enhances the binding and activity of CB agonists. GAT229 (1 μM) enhances the binding of the CB1 full agonist CP 55,940 to CHO cells expressing human recombinant CB1 (hCB1), as well as the activity of 2-arachidonoyl glycerol , arachidonoyl ethanolamide , and CP 55,940 in arrestin2 recruitment assays and increases ERK1/2 and PLCβ3 phosphorylation in HEK293 cells expressing hCB1. GAT229 (1 μM) enhances depolarization-induced suppression of excitation but does not inhibit excitatory postsynaptic currents (EPSCs) in murine autaptic hippocampal neurons. GAT229 (0.2%, topical) reduces intraocular pressure by 5.8 and 7.7 mm Hg after 6 and 12 hours, respectively, in a transgenic mouse model of ocular hypertension using nose, ear, eye mutation (nee) mice.

AL 8810 is an 11β-fluoro analog of prostaglandin F2α (PGF2α) which acts as a potent and selective antagonist at the FP receptor. AL 8810 ethyl amide is an analog of AL 8810 in which the C-1 carboxyl group has been modified to an N-ethyl amide. This modification is analogous to the PG N-ethyl amides, as typified by Bimatoprost, that have been introduced as alternative PG ocular hypotensive prodrugs. In contrast to AL 8810 which contracted the cat iris, AL 8810 ethyl amide showed no contraction activity at concentrations up to 10-4 M and did not antagonize the activity of PGF2α-ethanolamide in this system.

Naphazoline nitrate is an α1-Adrenergic receptor agonist. It also induces autophagy and necrotic cell death in erythroleukemia cells and inhibits erythroid differentiation. It used to treat congestion and ocular pathologies.

Difluprednate (Myser)(Durezol) is a corticosteroid, approved for the treatment of post-operative ocular inflammation and pain.

Aminozolamide is a carbonic anhydrase inhibitor that may be useful in the treatment of ocular hypertension.

Levobetaxolol, also known as AL-1577A and Betaxon, is a cardioselective β-adrenergic receptor inhibitor. It has been demonstrated to reduce intraocular pressure in patients affected by ocular hypertension and primary open-angle glaucoma.

Valacyclovir hydrochloride hydrate is a potent antiviral agent, a prodrug that is rapidly converted to acyclovir in vivo. valacyclovir hydrochloride hydrate can be used to formulate ocular inserts for the treatment of ocular herpes. valacyclovir hydrochloride hydrate is used in the treatment of herpes simplex, herpes zoster and herpes b.

Δ17-6-keto Prostaglandin F1α (Δ17-6-keto PGF1α), a cyclooxygenase (COX) metabolite produced from eicosapentaenoic acid (EPA) in a variety of tissues including seminal vesicles, lungs, polymorphonuclear leukocytes, and ocular tissues, alongside other 3-series COX products from EPA such as PGF3α, PGE3, and thromboxane B3, is potentially linked to a lower occurrence of glaucoma in individuals consuming a marine-rich (EPA-rich) diet.

Prostaglandin F2αethyl amide (PGF2α-NEt), a PGF2α analog featuring an N-ethyl amide modification at the C-1 carboxyl group, possesses ocular hypotensive activity similar to PG esters. Introduced as alternative prostaglandin ocular hypotensive prodrugs, PGF2α-NEt and other PG N-ethyl amides, contrary to claims of not converting to free acids in vivo, have been demonstrated by our laboratory studies to undergo conversion by bovine and human corneal tissue into the respective free acids at a rate of approximately 2.5 µg/g corneal tissue/hr. This suggests PGF2α-NEt is expected to elicit typical PGF2α free acid intraocular effects, albeit with slower hydrolysis kinetics characteristic of PG N-amides.

GAT564 (Compound 15d) is a highly effective allosteric modulator of cannabinoid 1 receptor (CB1R), having EC50 values of 87 nM and 320 nM for cAMP and β-arrestin2, respectively. It significantly enhances the binding of orthosteric ligands to hCB1R. Moreover, GAT564 exhibits remarkable efficacy as a topical agent, resulting in a significant reduction of intraocular pressure (IOP) in an ocular normotensive murine model of glaucoma [1].

KRFK, a peptide originating from TSP-1, activates TGF-β and facilitates TGF-β-mediated signaling pathways, independently of thrombospondin (TSP) receptors like CD47 and CD36. This property makes KRFK a potential research tool for chronic ocular surface inflammatory disorders [1].

Unoprostone isopropyl, a prostanoid and synthetic docosanoid, is approved for the treatment of ocular hypertension and open-angle glaucoma.

Fluprostenol is an F-series prostaglandin analog which has been approved for many years as a luteolytic in veterinary animals. The isopropyl ester of fluprostenol (travoprost) is an effective ocular hypotensive drug. CAY10532 is a methyl ester analog of fluprostenol.

Bimatoprost grenod(15-(6-nitroxyhexanoyl)-17-phenyl trinor PGF2α) is a nitric oxide-donating derivative of 17-phenyl trinor PGF2α.1It increases cGMP levels in rabbit aqueous humor and iris ciliary body when topically administered at a concentration of 0.042%. Topical administration of 15-(6-nitroxylhexanoyl)-17-phenyl trinor PGF2α(0.14%) reduces intraocular hypertension (IOP) in a rabbit model of hypertonic saline-induced transient ocular pressure. It also reduces IOP in a cynomolgus monkey model of laser-induced ocular hypertension when administered topically at a concentration of 0.042%.

17-phenyl trinor Prostaglandin F2α N-ethyl amide (17-phenyl trinor PGF2α) is an F-series prostaglandin analog which has been approved for use as an ocular hypotensive drug, sold under the Allergan trade name 17-phenyl trinor PGF2α ethyl amide. Investigations in our lab have shown that 17-phenyl trinor PGF2α ethyl amide is converted by an amidase enzymatic activity in the human cornea to yield the corresponding free acid, with a conversion rate of about 25 μg/cornea/24 hours. The free acid, 17-phenyl trinor PGF2α, is a potent FP receptor agonist. 15(R)-17-phenyl trinor PGF2α is the 15-epi, or unnatural isomer of this active free acid metabolite. It has much diminished FP receptor-mediated activity

KR-67607, also known as NTX-101 is novel selective 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) inhibitor. KR-67607 decreased 4-hydroxynonenal expression and increased antioxidant and mucus secretion in BAC-treated rat eyes. KR-67607 showed its protective effects against ischemia-reperfusion-induced eye injury. KR-67607 effectively reduced cortisol levels in mouse eyes and maintained the trabecular meshwork (TM) structure in the presence of transient ischemic stress. Furthermore, KR-67607 reversed the elevation of intra-ocular pressure (IOP), suggesting that the TM structure maintained by KR-67607 prevented the excessive rise in IOP that exacerbates glaucoma.

Latanoprost is an F-series prostaglandin (PG) analog which has been approved for use as an ocular hypotensive drug. Oxidation of the C-15 hydroxyl group without isopropyl ester hydrolysis produces 15-keto latanoprost. 15-keto Latanoprost is a potential metabolite of latanoprost when administered to animals. 15-keto Latanoprost is also one of the common minor impurities found in commercial preparations of the bulk drug compound. Although much less potent that the parent compound latanoprost, 15-keto latanoprost still retains the ability to produce a small but measurable decrease (1 mm Hg) in the intraocular pressure of normal cynomolgus monkeys when administered at a dose of 1 μg/eye. 15-keto Latanoprost is also a miotic in the normal cat eye, causing an 8 mm reduction in pupillary diameter at 5 μg/eye. Again, this is not as potent as many other F-type PGs; for example, PGF2α will produce this degree of miosis at a dose of less than 1 μg/eye. Products of β-oxidation account for most of the metabolites of latanoprost recovered in plasma and urine. However, 15-keto latanoprost is a minor metabolite, and one which could be enhanced in situations where β-oxidation is reduced.

Bromfenac Sodium (AHR 10282R) is a nonsteroidal anti-inflammatory drug (NSAID), which has anti-inflammatory activity and may block prostaglandin synthesis by inhibiting cyclooxygenase 1 and 2.

Bunazosin is a potent and selective α1-adrenoceptor antagonist that can be used for antihypertensive and ocular hypotensive research [1].

Ketorolac (RS37619) hemicalcium is a nonselective COX inhibitor with IC50s of 20 nM and 120 nM for COX-1 and COX-2, respectively. Ketorolac hemicalcium is a non-steroidal anti-inflammatory drug (NSAID) that is used as 0.5% ophthalmic solution for the research of allergic conjunctivitis, cystoid macular edema, intraoperative miosis, and postoperative ocular inflammation and pain. Ketorolac hemicalcium is also a DDX3 inhibitor that can be used in cancer research [1] [4].

Lifitegrast sodium (SAR-1118-023 sodium) is a small molecule integrin antagonist that inhibits T cell-mediated inflammation by blocking the binding of two important cell surface proteins (lymphocyte function-associated antigen 1 and intercellular adhesion molecule 1), which reduces inflammation of the ocular surface, and may be used in the study of dry eye.

Tropicamide (Ro 1-7683) is a synthetic muscarinic antagonist with actions similar to atropine and with an anticholinergic property. Upon ocular administration, tropicamide binds to and blocks the muscarinic receptors in the sphincter and ciliary muscle in the eye. This inhibits the responses from cholinergic stimulation, producing dilation of the pupil and paralysis of the ciliary muscle. Tropicamide is a diagnostic agent and is used to produce short-duration mydriasis and cycloplegia.

Fluprostenol isopropyl ester, a potent agonist of the F-series prostaglandin receptor, serves as a prodrug utilized clinically as an ocular hypotensive agent for glaucoma treatment. An impurity, 13(R),14(R)-epoxy fluprostenol isopropyl ester, arises during its production, existing as a chiral enantiomer of the epoxide. The pharmacological properties of this specific enantiomer have yet to be thoroughly investigated.

Bimatoprost (AGN 192024) is a cloprostenol-derived amide that is used as an antihypertensive agent in the treatment of open-angle glaucoma and ocular hypertension.