Visual System Disease

SH-11037 is a potent inhibitor of soluble epoxide hydrolase (sEH) and docks to the substrate binding cleft in the sEH hydrolase domain. SH-11037 dose-dependently suppresses angiogenesis in the choroidal sprouting assay ex vivo and inhibited ocular developmental angiogenesis in zebrafish larvae. SH-11037 reduces choroidal neovascularisation lesion volume in the laser-induced CNV mouse model. SH-11037 synergises with anti-VEGF treatments in vitro and in vivo. SH-11037 induces G2/M phase blockade and retains retinal endothelial cell viability at active concentrations without overt toxicity. SH-11037 can be used for the research of retinal neovascularization and ocular neovascularization.

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.

Aminozolamide is a carbonic anhydrase inhibitor. Aminozolamide regulates intraocular pressure by inhibiting carbonic anhydrase activity. Aminozolamide exerts local ocular effects, exhibits good retention in the ciliary body of rabbit eyes, and prevents rapid elimination from the eye. Aminozolamide is applicable to the research of ocular hypertension.

BI-1124 is a cathepsin S inhibitor that exhibits simulated sufficient ocular pharmacokinetic-pharmacodynamic coverage in rabbit models via topical ocular administration. BI-1124 can be used for the research of age-related dry eye disease.

5,7-Dihydroxytryptamine (5,7-DHP) is an autofluorescent (λ_ex≈365 nm), selective neurotoxin and a transport substrate for MAO-A and 5-HT. 5,7-Dihydroxytryptamine can specifically target and damage central and peripheral 5-HTergic neurons, while affecting 5-HT-related pathways and neurotransmitter balance. 5,7-Dihydroxytryptamine can be used to establish 5-HTergic neuron injury models for studies on neural development, neurodegenerative diseases, as well as mechanisms related to platelet function and retinal neurons.

Retinyl linoleate is a retinyl ester. Retinyl linoleate is synthesized by microsomes from Retinoic acid (HY-14649)-treated cultured human keratinocytes.

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.

GW559090 is a selective, competitive, and high-affinity α4 integrin antagonist with a K_d of 0.19 nM for α4β1. GW559090 can effectively block the binding of α4β1 to vascular cell adhesion molecule 1 (VCAM-1) and fibronectin with IC₅₀ values of 7.72 and 8.04 nM. GW559090 also inhibits the interaction between α4β7 and mucosal addressin cell adhesion molecule 1 (MAdCAM-1) (IC₅₀ = 23 nM). GW559090 can inhibit inflammatory infiltration in the eyes, repair the corneal barrier and restore the function of goblet cells. GW559090 can be used for research of Sjögren's syndrome associated dry eye.

PROTAC BRD3 degrader-1 (compound D072) is a potent and selective PROTAC BRD3 degrader. PROTAC BRD3 degrader-1 selectively degrades BRD3 in mice, leading to the downregulation of H3K18ac without affecting BRD2 or BRD4. PROTAC BRD3 degrader-1 reduces intraocular inflammation in the experimental autoimmune uveitis (EAU) mouse mode and inhibits proinflammatory microglia in both uveitis retina and LPS (HY-D1056) treated mouse microglia cell line BV2. PROTAC BRD3 degrader-1 can be used for uveitis research.

CAII-IN-11 (Compound A1) is a dual-target compound that contains a hCA II inhibitor (IC₅₀ = 2 nM) portion and a NO donor portion. CAII-IN-11 also has inhibitory activity against hCA IX, hCA XII, and hCA I, with IC₅₀ values of 6, 3, and 152 nM respectively. CAII-IN-11 significantly increases the intracellular cGMP level in human trabecular meshwork cells. CAII-IN-11 reduces the apoptosis of retinal ganglion cells by reducing oxidative stress (ROS levels), inhibiting astrocytes and the NLRP3 inflammasome activation. CAII-IN-11 has hypotensive activity in rabbit models and can be used for the study of glaucoma.

LFA-1-IN-2 (Compound 25) is a potent LFA-1 inhibitor with a K_d of 21.46 μM. LFA-1-IN-2 inhibits ICAM-1-mediated cell adhesion. LFA-1-IN-2 protects cells from inflammatory hyperosmotic stress. LFA-1-IN-2 improves dry eye disease.

Grp94-IN-3 (Compound 47) is a selective ATP competitive inhibitor of Grp94, with a K_d value of 76 nM. Grp94-IN-3 has a much lower affinity for Hsp90α, with a K_d value of 9.17 μM. Grp94-IN-3 induces the degradation of integrin α2 (Integrin α2) in MDA-MB-231 cells and reduces the intracellular accumulation of mutant cardiac proteins in human trabecular meshwork cells. Grp94-IN-3 can be used for the study of metastatic cancer and open-angle glaucoma.

Lortalamine (LM 1404) is a selective norepinephrine transporter inhibitor with an IC₅₀ of <1 nM. Lortalamine is a non-tricyclic antidepressant. Lortalamine antagonises Reserpine (HY-N0480)-induced ptosis and hypothermia. Lortalamine inhibits norepinephrine uptake.

Sezolamide (MK 417 free base) is a potent topical carbonic anhydrase inhibitor. Sezolamide can be used in studies to reduce intraocular pressure.

8-Iso-17-phenyl trinor prostaglandin F2α (8-Iso-17-phenyl trinor PGF2), the C-8 epimer of Bimatoprost (HY-B0191), is a PGF_2α (HY-12956) analog. Bimatoprost can be used in the research of glaucoma and high intraocular pressure.

UAMC-00050 free base is a potent trypsin-like serine protease inhibitor. UAMC-00050 free base can be used in research of dry eye syndrome and ocular inflammation.

Umbelopsisin A is a GABA_A and GABA_B non-selective agonist. Umbelopsisin A activates the GABAergic pathway, including notch signaling and fatty acid metabolism. Umbelopsisin A shows dual neuroprotection against glutamate excitotoxicity in vitro (reducing ROS and cell death) and in vivo. Umbelopsisin A can be used for the study of glaucoma and broader neurodegenerative disease applications.

SB772077B is a ROCK inhibitor. SB772077B has an anti-inflammatory activity and enhances aqueous outflow facility (OF) by inactivating RhoA/ROCK signal pathway. SB772077B significantly reduces the mRNA level of β-catenin and protein level of fibrotic markers, such as vinculin, fibronectin, collagen 1 A and vimentin. SB772077B also has vasodialatory activity and decreases pulmonary and systemic blood pressure. SB772077B can be used for glaucoma research and pulmonary hypertensive disorder research.