Glaucoma

ML-7 hydrochloride is a selective and highly specific myosin light chain kinase (MLCK) inhibitor that acts as a trabecular meshwork (TM) relaxant. ML-7 hydrochloride enhances Quinocetone (HY-123581)-induced phosphorylation of ERK, p38 MAPK and JNK, attenuates Akt activation, and promotes apoptosis of hepatocellular carcinoma cells. ML-7 hydrochloride reduces Th2 cytokine secretion by inhibiting MLCK, while alleviating smooth muscle hyperplasia and collagen deposition. As a non-antibiotic adjuvant, ML-7 hydrochloride restores the sensitivity of drug-resistant bacteria to Tigecycline (HY-B0117). ML-7 hydrochloride can be used in research related to glaucoma, hepatocellular carcinoma, asthma, and Klebsiella pneumoniae infection.

Xelafaslatide (ONL-1204) is a Fas receptor antagonist. Xelafaslatide blocks the Fas receptor signaling pathway and inhibits downstream apoptosis and inflammatory pathways. Xelafaslatide suppresses neuroinflammation and microglial activation in glaucoma models, protects retinal ganglion cells and prevents axonal degeneration. Xelafaslatide is applicable to relevant research on glaucoma.

Arundic Acid is an orally effective astrocyte function modulator and neuroprotective agent. Arundic Acid increases the expression and function of the astrocytic glutamate transporter EAAT1 by activating the ERK, Akt and NF-κB pathways. Arundic Acid attenuates retinal ganglion cell death in a normal-tension glaucoma model. Arundic Acid exerts neuroprotective effects in a mouse model of Parkinson's disease. Arundic Acid is a S100β protein synthesis inhibitor that prevents neurological deficits and brain tissue damage after intracerebral hemorrhage in rats. Arundic Acid downregulates neuroinflammation and astrocytic dysfunction after status epilepticus in immature rats. Arundic Acid is applicable to research related to Parkinson's disease, cerebral ischemia, glaucoma, intracerebral hemorrhage and epilepsy.

Clemastine (HS-592; Meclastine) is an orally active, blood-brain barrier-permeable H1 histamine receptor (H1 histamine receptor) antagonist with potent antiallergic effects. Clemastine also antagonizes muscarinic acetylcholine receptors (mAChR), particularly the M1 and M4 subtypes. In addition to antihistamine effects, Clemastine exhibits multiple pharmacological activities, especially in promoting central nervous system remyelination, activating autophagy and pyroptosis, exerting anti-apoptotic and neuroprotective effects, and suppressing inflammation.

Latanoprostene bunod (NCX116; LBN) is a nitric oxide-releasing prostaglandin F₂α analog. Latanoprostene bunod is a prodrug that, upon instillation into the eye, is hydrolyzed by corneal esterases into two active metabolites: Latanoprost (HY-B0577) and NO. Latanoprost activates the prostaglandin FP receptor to increase the outflow of aqueous humor through the uveoscleral pathway. NO increases aqueous humor drainage through the trabecular meshwork pathway, achieving synergistic enhancement targeting the dual pathways of aqueous humor outflow. Latanoprostene bunod can be used in research related to open-angle glaucoma and ocular hypertension.

TH251 is a LIMK1 and LIMK2 inhibitor with IC₅₀s of 52 nM and 47 nM against LIMK1 and LIMK2, respectively. TH251 binds to inactive αC-out and DFG-out LIMK1 conformations, inhibits unphosphorylated LIMK1 and LIMK2 enzymatic activity, and exhibits unchanged potency despite PAK-mediated phosphorylation of either kinase. TH251 can be used for the research of cancers, glaucoma, and CNS diseases.

CP-432 (CP-734432) is a EP4 receptor agonist with an IC₅₀ of 2 nM for human sources, 8 nM for canine sources, and an EC₅₀ of 1 nM for human sources. CP-432 stimulates cAMP production and activates β-lactamase (β-lactamase) activity via the cAMP response element signaling pathway. CP-432 is applicable to research related to glaucoma.

KUNG94 is a selective Grp94/HSP90B inhibitor (IC₅₀=8 nM). By inhibiting the chaperone function of Grp94, KUNG94 reduces the maturation and cell surface trafficking of its specific client proteins. KUNG94 can be used for studies on Grp94-related biological mechanisms, as well as diseases including cancer and primary open-angle glaucoma.

Pegsebrenatide (NLY01) is a blood-brain barrier-penetrant GLP-1R agonist. Pegsebrenatide alleviates retinal inflammation and neuronal death secondary to ocular hypertension. Pegsebrenatide significantly delays onset and reduces disease severity in experimental autoimmune encephalomyelitis. Pegsebrenatide inhibits the formation of A1 reactive astrocytes in nerve cells and reduces the loss of retinal ganglion cells and dopaminergic neurons. Pegsebrenatide exerts neuroprotective effects in a mouse model of Parkinson's disease by directly preventing microglia-mediated conversion of astrocytes to the A1 neurotoxic phenotype. Pegsebrenatide can be used for research on glaucoma, Parkinson's disease, and multiple sclerosis.

Sepetaprost (ONO-9054) is a dual agonist of the prostaglandin E3 receptor and prostaglandin F receptor. Sepetaprost reduces intraocular pressure in animal models. Sepetaprost is applicable for research on ocular hypertension and open-angle glaucoma.

CAII-IN-16 is a selective inhibitor of carbonic anhydrase II (CA II), with an IC₅₀ of 0.5 nM against hCA II. CAII-IN-16 exhibits excellent intraocular pressure-lowering activity in a rabbit glaucoma animal model. CAII-IN-16 can be used for the research of glaucoma.

A3AR antagonist-8 is a selective A3 adenosine receptor antagonist with a K_i of 98 nM for human A3 adenosine receptor. A3AR antagonist-8 can be used for the research of glaucoma, chronic renal disease, acute renal ischemia and reperfusion injury, and cancer.

PF-04475270 is a prodrug of CP-734432 (HY-119236), as well as an agonist of the EP4 prostaglandin receptor, with IC₅₀ values of 2 nM and 8 nM against human and canine sources, respectively. PF-04475270 is rapidly hydrolyzed into its active metabolite CP-734432 by ocular esterases or corneal homogenate, stimulates cAMP production, and activates cAMP response element-mediated β-lactamase activity in cells expressing EP4. PF-04475270 can be used in research related to glaucoma.

CAII-IN-15 is a potent carbonic anhydrase II (CA II) inhibitor with a hCA II IC₅₀ of 10 nM. CAII-IN-15 elevates cGMP levels, releases nitric oxide, reduces oxidative stress, and exhibits neuroprotective activity in vitro. CAII-IN-15 inhibits NLRP3 inflammasome activation, reduces neuronal apoptosis. CAII-IN-15 reduces Intraocular pressure (IOP) in rabbits. CAII-IN-15 can be used for the research of glaucoma.

Neuro-DiO 4-chlorobenzenesulfonate is a hydrophobic C₁₈ alkyl chain carbocyanine dye with green fluorescence, commonly used as a vascular marker, cell internalizer and deposition agent. Neuro-DiO 4-chlorobenzenesulfonate inserts its alkyl chain into the endothelial plasma membrane via liposome-mediated perfusion to achieve vascular labeling. Neuro-DiO chlorobenzenesulfonate can also stain the cell membrane and cytoplasm of cancer cells to assist in confocal microscopy observations. Neuro-DiO chlorobenzenesulfonate can be released from nanosponges and accumulate on the surface of mouse retina, then internalize into retinal ganglion cells, which is applicable to researches related to glaucoma and other diseases. It should be noted that during liposome-mediated vascular staining in mice, Neuro-DiO 4-chlorobenzenesulfonate may cause leakage of airway lavage fluid.

ICI 147798 is an orally effective β-adrenoceptor antagonist with a pK_B of 9.1 (in guinea pig right atrium) and 8.8 (in guinea pig trachea). ICI 147798 acts as a diuretic and intraocular pressure-lowering agent. ICI 147798 blocks β-adrenoceptors, inhibits isoproterenol-induced tachycardia and vasodepressor responses, exhibits slowly dissociating, insurmountable antagonism against β₁-adrenoceptors, and shows surmountable competitive antagonism against β₂-adrenoceptors. ICI 147798 induces natriuresis and kaliuresis, inhibits sodium transport, and reduces intraocular pressure.

AL-6556 is a full agonist of the DP receptor and a partial agonist of the EP2 receptor. AL-6556 has an EC₅₀ of 799 nM for bovine DP, a K_i of 3200 nM for human DP, and an EC₅₀ of 1180 nM for human EP2, with selectivity over EP3, FP, IP, TP and 19 non-prostaglandin receptors. AL-6556 stimulates cAMP production via receptor activation and reduces intraocular pressure through aqueous humor inflow and outflow mechanisms. AL-6556 can be used in research related to ocular hypertension and glaucoma.

NCX-278 is a human carbonic anhydrase inhibitor with a 13 nM K_i for hCA II, 410 nM K_i for hCA I, 181 nM K_i for hCA IV, and selective inhibition of hCA II over hCA IV. NCX-278 is a potent and effective stimulator of NO/sGC/cGMP signaling with an EC₅₀ of 2.05 lM. NCX-278 exerts NO-mediated vascular relaxant effects. NCX-278 lowers intraocular pressure in normotensive rabbits. NCX-278 can be used for the research of open-angle glaucoma.

AL-38022A is a potent and selective 5-HT₂ receptor agonist (K_i ≤2.2 nM), but a significantly lower (>100-fold less) affinity for other 5-HT receptors. AL-38022A potently stimulates functional responses via 5-HT₂ receptor subtypes including [Ca²⁺]_i mobilization and tissue contractions with apparently similar potencies and intrinsic activities. AL-38022A fully generalizes to the (±)-1-(2,5-dimethoxy 4-methylphenyl)-2-aminopropane hydrochloride (DOM) stimulus in drug discrimination paradigms. AL-38022A can be used for the glaucoma research.

CAI-IN-6 (Compound 3F) is a carbonic anhydrase (CAI) inhibitor with a K_i of 902.1 nM against hCA I and a K_i of 86.1 nM against hCA II. CAI-IN-6 can be used for the research of diuresis, glaucoma, epilepsy, tumors, and other conditions.