Carbonic Anhydrase

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.

Methyl 2,4-dihydroxybenzoate is a natural product.

Benzenesulfonamide (Benzosulfonamide) ia an inhibitor of carbonic anhydrases.

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.

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.

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.

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.

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.

Carbonic anhydrase inhibitor 6 is a potent human carbonic anhydrase (hCA) inhibitor that inhibits hCA IX, hCA II, hCA XII, and hCA I. It is used in the study of diseases caused by abnormalities in carbonic anhydrase.

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

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.

hCAI/II/IV-IN-28(WAY-638358) is a potent carbonic anhydrase inhibitor with potential anticonvulsant activity.

hCAII-IN-9 is a potent carbonic anhydrase inhibitor that inhibits hCA II, hCA IX, and hCA XII with IC50s of 1.18 μM and 0.17 μM , and 2.99 μM , respectively. hCAII-IN-9 is not blood-brain barrier permeable.

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

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.

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

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.

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

Ellagic acid (Gallogen) is a fused four ring compound isolated from the kino of Eucalyptus maculata Hook and E. Hemipholia F. Muell. Activates Factor XII of the blood clotting system which also causes kinin release; used in research and as a dye.

Acetazolamide (Diamox) is a Carbonic Anhydrase Inhibitor. The mechanism of action of acetazolamide is as a Carbonic Anhydrase Inhibitor. The chemical classification of acetazolamide is Sulfonamides.

Compound 1e, also known as ALP/Carbonic anhydrase-IN-1, is a dual inhibitor targeting both carbonic anhydrase (CA) isozymes II, IX, and XII, as well as alkaline phosphatase (ALP). It exhibits inhibitory IC50 values of 0.44 µM for CA-II, 1.61 µM for CA-IX, 0.51 µM for CA-XII, and 0.107 µM for ALP [1].

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

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.

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

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.

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

Chlorothiazide (Diuril) is a thiazide diuretic with actions and uses similar to those of HYDROCHLOROTHIAZIDE.

Bendroflumethiazide (Naturetin) is a thiazide diuretic with actions and uses similar to those of HYDROCHLOROTHIAZIDE. It has been used in the treatment of familial hyperkalemia, hypertension, edema, and urinary tract disorders. (From Martindale, The Extra Pharmacopoeia, 30th ed, p810)

Enpp Carbonic anhydrase-IN-1 (compound 1e) is a potent inhibitor of Enpp and carbonic anhydrase. Enpp Carbonic anhydrase-IN-1 exhibits 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 exhibits selective antiproliferative activity for cancer cells.

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

Compound 4d, known as hCA XII-IN-6, is a potent inhibitor of human carbonic anhydrase XII (hCA XII) with a Ki value of 84.2 nM and exhibits anti-proliferative effects, making it useful in cancer research [1].

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.

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.

Compound 3e (hCAIX/XII-IN-7) is a potent inhibitor of human carbonic anhydrase (hCA) isozymes IX and XII, displaying inhibitory constants (Kis) of 503.7 nM for hCA IX and 59 nM for hCA XII, while also showing activity against hCA I and II with Kis of 3.2 nM and 9.2 nM, respectively. It holds potential for research into hypoxic tumors [1].

Tioxolone is a metalloenzyme carbonic anhydrase I inhibitor.

hCAIX-IN-16 (Compound 12d), an inhibitor of hCA IX, exhibits inhibition constants (K i) of 190.0 nM for hCA IX and 187.9 nM for hCA XII. It can arrest the cell cycle in the G0-G1 and S phases and induce apoptosis in MDA-MB-468 breast cancer cells. Demonstrating broad-spectrum anticancer activity, hCAIX-IN-16 is a potential tool for cancer research [1].

Halazone (Pantocid) is fine white powder with an odor of chlorine. It has been widely used to disinfect drinking water.

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

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).

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.

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.

hCAIX/VII-IN-1 is a selective inhibitor of human carbonic anhydrase isoforms VII and IX. It displays inhibitory activity against hCA I, II, IV, VII, and IX, with respective K_i values of 336.2 nM, 185.8 nM, 1055 nM, 35.6 nM, and 28.0 nM. This compound is applicable in cancer and neurological disease research [1].

hCAXII-IN-7 (compound 6e) functions as an inhibitor of human carbonic anhydrase XII (hCA XII) and possesses blood-brain barrier (BBB) permeability. Moreover, it promotes apoptosis in 786-0, SF-539, and HS 578 T cell lines [1].

hCA/VEGFR-2-IN-1 (compound 13a) is a potent dual inhibitor targeting both Carbonic Anhydrase (CA) IX/XII and Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2). It exhibits Ki values of 4.7 nM for hCA XII and 8.3 nM for hCA IX, alongside an IC50 of 26.3 nM for VEGFR-2. This compound demonstrates anticancer activity [1].

hCAIX/XII-IN-8 (compound 3g) is a potent inhibitor of the human carbonic anhydrases (CAs) IX and XII, with inhibition constants (K i) of 8.5 nM for CA IX and 6.7 nM for CA XII. It demonstrates significant inhibitory efficacy particularly against tumor-associated, membrane-bound isoforms hCA IX and XII, while exhibiting a high selectivity over the cytosolic isoforms hCA I and II [1].

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.

Carbonic Anhydrase Inhibitor 12 is a potent inhibitor of CA II, with additional inhibitory activity against CA I, exhibiting K_i values of 1.72 nM for CA II and 271 nM for CA I. Moreover, it demonstrates significant anticancer activity across various cancer cell lines [1].

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

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.

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.