Carbonic Anhydrase

EMD57033 is a cardiac troponin C (cTnC) activator, a dominant Ca2+ sensitizer, which functions by binding to cardiac slow skeletal troponin C heterodimers to promote cardiac contraction.

Indisulam (E 7070) is a carbonic anhydrase inhibitor and antitumor CDK inhibitor that targets the G1 phase of the cell cycle by depleting cyclin E, inducing p53 and p21, and inhibiting CDK2, thereby causing a blockade in the G1 S transition.

Ellagic acid (Gallogen), a thickened tetracyclic natural product, is a potent CK2 inhibitor (IC50=40 nM; Ki=20 nM) with ATP-competitive properties. Ellagic acid is an antioxidant and also possesses antiproliferative activity.

Levosimendan (OR1259) is a calcium sensitizer used in the management of acutely decompensated congestive heart failure. It increases the sensitivity of the heart to calcium, thus increasing cardiac contractility without a rise in intracellular calcium. Levosimendan exerts its effect by increasing calcium sensitivity of myocytes by binding to cardiac troponin C in a calcium-dependent manner.

1. Eriocitrin (Eriodictyol-7-O-Rutinoside) is powerful antioxidative flavonoid; (1) Prevents oxidative damages caused by acute exercise-induced oxidative stress.(2) Lipid-lowering effects in a rat model of high-fat diet. 2. Dietary Eriocitrin ameliorates diet-induced hepatic steatosis with activation of mitochondrial biogenesis. 3. Eriocitrin and Apigenin were identified as new potent inhibitors of human carbonic anhydrase VA isozyme.

hCAIX-IN-5 was a selective hCAIX inhibitor, inhibiting hCAI, hCAII, hCAIV, and hCAIX with Ki values of >10000, >10000, 130.7, and 829.1 nM, respectively.

CAIX Inhibitor S4 (S4) is an effective inhibitor of carbonic anhydrase IX XII with a Ki of 7 nM and 2 nM, respectively. The Kis for CA II and CA I are 546 and 5600 nM.

Ethoxzolamide (L-643786) is a carbonic anhydrase inhibitor.

Zonisamide (AD 810), a sulfonamide anticonvulsant, is approved for use as an adjunctive treatment in adults with partial-onset seizures. It may inhibit a carbonic anhydrase although this is not one of the main mechanisms of action. Zonisamide may act by blocking repetitive firing of voltage-gated sodium channels results in a reduction of T-type calcium channel currents, or by binding allosterically to GABA receptors. This latter action may lower the uptake of the inhibitory neurotransmitter GABA while increasing the uptake of the excitatory neurotransmitter glutamate.

Benzolamide (CL 11366) inhibits carbonic anhydrase effectively and low-threshold calcium currents in hippocampal pyramidal neurons.

Sultiame is an inhibitor of carbonic anhydrase. Sultiame can be used in antiepileptic research.

U-104 (NSC-213841) is an effective carbonic anhydrase (CA) inhibitor for CA IX( Ki=45.1 nM) and CA XII(Ki=4.5 nM).

4-Amino-6-(trifluoromethyl)benzene-1,3-disulfonamide (4-Amino-6-(trifluoromethyl)benzene-1,3-d) is a carbonic anhydrase inhibitor, used as a potential anti-tumor and antiglaucoma drug.

Acetazolamide sodium (OT-302 sodium) is a potent carbonic anhydrase (CA)IX inhibitor with diuretic, antigonococcal, and antihypertensive activity and may be used for indications such as epilepsy, glaucoma, edema, and altitude sickness.

Girentuximab (G250) is a potent anti-carbonic anhydrase IX (CAIX) monoclonal antibody with anticancer activity for the study of uroepithelial carcinoma PET (ZiPUP).

Topiramate (RWJ 17021) is a unique antiseizure medication that is used in the treatment of partial and generalized seizures. Topiramate has been rarely associated with hepatic injury and largely when used in combination with other anticonvulsant medications.

Methyclothiazide (Aquatensen) is a substituted benzothiadiazide, used to treat high blood pressure and fluid retention caused by various conditions including heart disease.

Dichlorphenamide (Diclofenamide) is a carbonic anhydrase inhibitor that is used in the treatment of glaucoma.

Taselisib (GDC-0032) is an orally bioavailable inhibitor of the class I phosphatidylinositol 3-kinase (PI3K) alpha isoform (PIK3CA), with potential antineoplastic activity.

pNNP (Nitrophenylphosphate) can be used as a substrate for the PP2C assay. pNNP inhibits β-carbonic anhydrase and α-carbonate dehydrogenase, as well as H. pylori Helicobacter pylori. pNNP is a weakly active, tissue-nonspecific alkaline phosphatase modifier. pNNP has been shown to inhibit β-carbonic anhydrase and α-carbonate dehydrogenase.

Mafenide hydrochloride (4-Aminomethylbenzenesulfonamide hydrochloride) is a sulfonamide that inhibits the enzyme carbonic anhydrase and is used as topical anti-infective, especially in burn therapy.

Benzenesulfonamide (Benzosulfonamide) ia an inhibitor of carbonic anhydrases.

Benzthiazide (Lemazide) is used in the therapy of edema and hypertension. Like other thiazides, benzthiazide accelerates water loss from the body (diuretics). They inhibit Na+ Cl- reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue.

Methazolamide (CL 8490) is a carbonic anhydrase inhibitor that is used as a diuretic and in the treatment of glaucoma.

Hydrochlorothiazide (HCTZ) is a Thiazide Diuretic. The physiologic effect of hydrochlorothiazide is by means of Increased Diuresis.

Dimethylfraxetin (6,7,8-Trimethoxycoumarin) is a Carbonic anhydrase inhibitor(Ki:0.0097 μM)

Polmacoxib (CG 100649) is a first-in-class NSAID drug candidate, is a dual inhibitor of carbonic anhydrase (CA) and COX-2. Polmacoxib inhibits premalignant and malignant colorectal lesions in mouse models, partly through inhibiting tumor cell proliferation.

hCAI II-IN-6 is a selective and orally active inhibitor of human carbonic anhydrase (CA). hCAI II-IN-6 inhibited hCA I, hCA II, hCA VII, and hCA XII with Ki values of 220, 4.9, 6.5, and ＞50,000 nM. hCAI II-IN-6 showed anticonvulsant activity in vivo. hCAI II-IN-6 can be used to study epilepsy. hCAI II-IN-6 showed anticonvulsant activity in vivo. hCAI II-IN-6 can be used to study epilepsy.

Urea (Carbonyldiamide) is formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end metabolite of protein catabolism and accounts for about one-half of the total urinary solids.

Dorzolamide hydrochloride (MK507 hydrochloride) is the hydrochloride salt form of dorzolamide, an inhibitor of carbonic anhydrase, a zinc-containing enzyme that catalyzes the rapid conversion of carbon dioxide and water into carbonic acid, protons and bicarbonate ions. Distributed throughout many cells and tissues, various carbonic anhydrases play important roles in mineral and metabolic homeostasis.

Trichlormethiazide (Naqua) is a short-acting, 3-dichloromethyl derivative of hydrochlorothiazide, belonging to the class of thiazide diuretics. Trichlormethiazide appears to block the active reabsorption of chloride and possibly sodium in the ascending loop of Henle, altering electrolyte transfer in the proximal tubule.

6-Hydroxycoumarin (6-hydroxychromen-2-one) exhibits cytotoxicity against human HL60, HCT116, COLO205 cells with activity value of 35 uM, 42 uM, 37 respectively. 6-Hydroxycoumarin is a human CA9, CA12 inhibitor.

Orthanilamide (Orthanilamide) is a molecule containing the sulfonamide functional group attached to an aniline.

Methocarbamol (AHR 85) is a centrally acting muscle relaxant whose mode of action has not been established. It is used as an adjunct in the symptomatic treatment of musculoskeletal conditions associated with painful muscle spasm.

Brinzolamide (AL-4862) is a Carbonic Anhydrase Inhibitor. Its mechanism of action involves inhibiting the enzyme Carbonic Anhydrase.

Fluorometholone Acetate (Oxylone acetate) is a synthetic corticosteroid, used in the treatment of steroid responsive inflammatory conditions of the eye.

Methyl 2,4-dihydroxybenzoate is a natural product.

Tioxolone is a metalloenzyme carbonic anhydrase I inhibitor.

PIK-93, the first potent synthetic PI4K inhibitor, exhibits an IC50 of 19 nM and also inhibits PI3Kα with an IC50 of 39 nM.

(Iso)-Samixogrel shows activity against Carbonic anhydrase and Cyclooxygenase 2.

Histone acetyltransferase p300 Inhibitor 4c is a 2-aminothiazole derivative. Histone acetyltransferase p300 Inhibitor 4c inhibited hCA I, hCA II, AChE and BChE with Ki values of 0.008 ± 0.001, 0.124 ± 0.017, 0.129 ± 0.030 and 0.083 ± 0.041 µM. 0.017, 0.129 ± 0.030 and 0.083 ± 0.041 μM.

Cyclamic acid sodium (Cyclohexylsulfamicacidsodium) is a carbonic anhydrase inhibitor and one of the most widely used artificial sweeteners in food and pharmaceuticals.Cyclamic acid sodium shows moderate anticonvulsant activity in a maximal electroshock convulsive seizure model.Cyclamic acid sodium is used in cancer research.

Enpp Carbonic anhydrase-IN-2 is a potent dual inhibitor of Enpp and carbonic anhydrase, inhibiting NPP1, NPP2, NPP3, CA-IX, CA-XII, with IC50 values of 1.13, 1.07, 0.74, 0.33, 0.68, respectively.Enpp Carbonic anhydrase-IN-2 induced apoptosis.Enpp Carbonic anhydrase-IN-2 has antiproliferative activity against cancer cells and low cytotoxicity against normal cells.

Compound CDy9 is a highly selective inhibitor of carbonic anhydrase (CA) with an IC50 value of 0.18 μM for hCA II.

2,3-dihydro-1H-indene-5-sulfonamide is Carbonic anhydrase 12 (human) inhibitor.

compound EMAC10101d, bearing a 2,4-dichorophenyl substituent in position 4 of the dihydrothiazole ring, was the most potent and selective toward hCA II with an inhibitory activity in the low nanomolar range.

hCAII-IN-9 is a potent carbonic anhydrase inhibitor with IC50 values of 1.18 μM for hCA II, 0.17 μM for hCA IX, and 2.99 μM for hCA XII. It is not blood-brain barrier permeable.

Enpp Carbonic anhydrase-IN-1 (compound 1e) is a potent inhibitor of Enpp and carbonic anhydrase, exhibiting IC50s of 1.36, 1.35, 3.00, 0.88, and 1.02 µM for NPP1, NPP2, NPP3, CA-II, and CA-IX respectively. Enpp Carbonic anhydrase-IN-1 also demonstrates selective antiproliferative activity for cancer cells.