CA Ⅱ Inhibitor

Methazolamide (L584601) is a BBB-penetrable and orally active carbonic anhydrase inhibitor, with a K_i of 14 nM for human carbonic anhydrase II. Methazolamide can reduce intraocular pressure and has a neuroprotective effect, being able to inhibit neuronal apoptosis. Methazolamide can be used in the research of ophthalmic diseases such as glaucoma and cerebrovascular diseases such as subarachnoid hemorrhage.

Zonisamide (AD 810) is an orally active carbonic anhydrase inhibitor, with K_is of 35.2 and 20.6 nM for hCA II and hCA V, respectively. Zonisamide exerts neuroprotective effects through anti-apoptosis and upregulating MnSOD levels. Zonisamide also increases the expression of Hrd1, thereby improving cardiac function in AAC rats. Zonisamide can be used in studies of seizure, parkinson’s disease and cardiac hypertrophy.

Brinzolamide (AL-4862) is a selective carbonic anhydrase II inhibitor with anIC₅₀ value of 3.2 nM. Brinzolamide hydrochloride reduces intraocular pressure (IOP) by inhibiting ciliary CA-II and decreasing atrial fluid secretion. Brinzolamide can be used in glaucoma disease research.

Dorzolamide (L671152) hydrochloride is a potent carbonic anhydrase II inhibitor, with IC₅₀ values of 0.18 nM and 600 nM for red blood cell CA-II and CA-I respectively. Dorzolamide possesses anti-tumor activity.

Benzolamide (CL11366) is a potent carbonic anhydrase (CA) inhibitor, with K_is of 15 nM, 9 nM, 94 nM and 78 nM for hCA I, hCA II, EcoCAγ and VchCAγ, respectively. Benzolamide also inhibits CAS3, with a K_i of 54 nM. Benzolamide can be used for the research of glaucoma and seizures.

COX-2/CA II-2 is an orally active dual selective inhibitor targeting COX-2 and hCA II. COX-2/CA II-2 inhibits COX-2 with an IC₅₀ value of 0.05 μM (SI = 12.02 vs COX-1) and hCA II with a K_i value of 62.6 nM (SI = 704.2 vs hCA I). COX-2/CA II-2 demonstrates significant analgesic and anti-inflammatory effects with rapid onset and sustained duration in animal models, shows improved gastric safety with reduced ulcerogenic liability, and exhibits a gradual intraocular pressure (IOP)-lowering effect without statistical significance relative to the sham-treated eye in rabbit glaucoma models. COX-2/CA II-2 can be used for anti-inflammatory, analgesic and antiglaucoma research.

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.

Methyl acetazolamide (Propazolamide) is a carbonic anhydrase inhibitor with K_i values of 37.5 nM against Enterococcus faecium α-CA, 250.1 nM against Enterococcus faecium γ-CA, 235.4 nM against human CA I, and 37.2 nM against human CA II. Methyl acetazolamide can be used for the research of enterococcus infections.

TAS4464 hydrochloride is a long-acting, highly selective covalent inhibitor targeting NEDD8-activating enzyme (NAE) (IC₅₀=0.955 nM), and also inhibits CAII with an IC₅₀ of 0.73 μM, which is less potent than MLN4924 (HY-70062). The IC₅₀ values of TAS4464 hydrochloride against other E1 enzymes UAE and SAE are 449 nM and 1280 nM, respectively. TAS4464 hydrochloride targets NEDD8 in an ATP-dependent manner to inhibit NAE, blocks the neddylation pathway, causes accumulation of CRL ubiquitin ligase substrates (such as CDT1, p27, phosphorylated IκBα), and further induces tumor cell apoptosis. TAS4464 hydrochloride exhibits antiproliferative and cytotoxic effects, and has broad-spectrum antitumor activity against various hematologic and solid tumor cell lines as well as patient-derived tumor cells. TAS4464 hydrochloride has a wide therapeutic window, without obvious toxicity. TAS4464 hydrochloride can be used in the research of hematologic malignancies (leukemia, lymphoma, multiple myeloma, etc.) and solid tumors (small cell lung cancer, colorectal cancer, sarcoma, endometrial cancer, ovarian cancer, etc.).

Benzenesulphonamide (Compound 1) is a carbonic anhydrase inhibitor. Benzenesulphonamide exhibits CA II inhibitory activity. Benzenesulphonamide reduces ROS and improves the gene expression of amyloid-β40 and 42. Benzenesulphonamide is beneficial for Alzheimer's disease. Benzenesulphonamide derivatives have anticancer, anti-inflammatory, and anticonvulsant activities. Benzenesulphonamide can be used in the research of Alzheimer's disease, epilepsy, inflammatory diseases, leukemia, melanoma, lung cancer, and colon cancer.

Carzenide (4-Sulfamoylbenzoic acid) is the major circulating metabolite of Mafenide (HY-B0614) in plasma. Carzenide is a strong CAII competitive inhibitor. Carzenide can be used in the research of epilepsy and cervical cancer.

Halazone is an atypical antimicrobial sulfonamide derivative and a carbonic anhydrase II inhibitor with a K_d value of 1.45 μM. Halazone protects sodium channels from inactivation. Halazone is widely used for disinfection of drinking water.

4-Chloro-3-sulfamoylbenzoic acid is a weak inhibitor of human carbonic anhydrase isoforms hCA I, hCA II, hCA IV, and hCA IX, and a synthesis intermediate for carbonic anhydrase inhibitors. 4-Chloro-3-sulfamoylbenzoic acid is the major metabolite of tripamide detected in tissues, urine, and feces of rats and rabbits following Tripamide (HY-106570) administration. 4-Chloro-3-sulfamoylbenzoic acid can be used for the study of carbonic anhydrase inhibition and species differences in drug metabolism.

Zonisamide-d₄ is the deuterium labeled Zonisamide. Zonisamide (AD 810) is an inhibitor of zinc enzyme carbonic anhydrase (CA), with K_is of 35.2 nM and 20.6 nM for human mitochondrial isozyme hCA II and hCA V, respectively. Zonisamide has antiepileptic activity. Zonisamide can be used for the rsearch for epilepsy, seizures and Parkinson's disease.

Carbonic anhydrase inhibitor 1 (compound 7c) is a carbonic anhydrase II inhibitor. Carbonic anhydrase inhibitor 3 reduces the intraocular pressure in glaucomatous rabbits.

hCAIX-IN-18 (compound 30) is an inhibitor of carbonic anhydrase (CA), with K_is of 3.5 nM, 9.4 nM, 43.0 nM and 8.2 nM for hCAI, hCAII, hCAIX, hCAXII, respectively. hCAIX-IN-18 can be used for cancer research.

Fluorometholone acetate is a synthetic glucocorticoid corticosteroid and a corticosteroid ester. Fluorometholone acetate potently inhibits carbonic anhydrase (CA) with IC₅₀s of 2.18 μM and 17.5 μM for hCA-I and hCA-II, respectively. Fluorometholone acetate has anti-inflammatory effect and has the potential for external ocular inflammation research.

EMAC10101d is a potent and selective toward hCA II inhibitor, with a K_i of 8.1 nM.

Enpp/Carbonic anhydrase-IN-1 (compound 1e) is a potent Enpp and carbonic anhydrase inhibitor with IC₅₀s of 1.36, 1.35, 3.00, 0.88, 1.02 μM for NPP1, NPP2, NPP3, CA-II, CA-IX respectively. Enpp/Carbonic anhydrase-IN-1 shows antiproliferative activity for cancer cells and low cytotoxic against normal cells. Enpp/Carbonic anhydrase-IN-1 induces Apoptosis.

hCAII-IN-8, an amide, is a highly selective carbonic anhydrase (CA) inhibitor with an IC₅₀ value of 0.18 μM against hCA II.