carbonic anhydrase

Carbonic anhydrase is ubiquitous zinc-containing metalloenzyme present in prokaryotes and eukaryotes. Carbonic anhydrase can catalyze reversible conversion of carbon dioxide to bicarbonate and protons. Carbonic anhydrase can be used for the research of cancer , glaucoma, obesity and epilepsy [1] [2] .

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.

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].

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.

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.

Compound 7c, identified as carbonic anhydrase inhibitor 1, effectively inhibits carbonic anhydrase II. This inhibitor, also known as carbonic anhydrase inhibitor 3, lowers intraocular pressure in glaucomatous rabbits [1].

Carbonic anhydrase inhibitor 8 (compound R-13) is a potent human carbonic anhydrase (hCA). Carbonic anhydrase inhibitor 8 shows K i values of 60.7 nM, 320.7 nM, 2298 nM for hCA I, hCA II, hCA IV, respectively.

Enpp/Carbonic anhydrase-IN-2 is a potent Enpp and carbonic anhydrase inhibitor with IC 50 s of 1.13, 1.07, 0.74, 0.33, 0.68 for NPP1, NPP2, NPP3, CA-IX, CA-XII respectively. Enpp/Carbonic anhydrase-IN-2 shows antiproliferative activity for cancer cells and low cytotoxic against normal cells. Enpp/Carbonic anhydrase-IN-2 induces Apoptosis .

Human carbonic anhydrase II-IN-24 (Compound R-13) is a potent human carbonic anhydrase (hCA) inhibitor. Human carbonic anhydrase II-IN-24 shows K i s of 60.7, 320.7, 2298, and 35.2 nM for hCA I, II, IV and IX, respectively.

Carbonic Anhydrase Inhibitor 15 (Compound 8), with an inhibitory constant (K_i) of 8.5 nM for hCA II, exhibits analgesic effects [1].

Carbonic anhydrase inhibitor 7 is a potent inhibitor of human carbonic anhydrase (hCA), acting on hCA IX (Ki: 6.5 nM), hCA II (Ki: 7.1 nM), hCA XII (Ki: 72.1 nM) and hCA I (Ki: 255.8 nM).

Human carbonic anhydrase II-IN-1 (Compound S-13) is a potent human carbonic anhydrase II (hCA II) inhibitor. Human carbonic anhydrase II-IN-1 shows Kis of 4.4 nM, 9.2 nM, 480.2 nM and 14.7 nM for hCA II, I, IV and IX, respectively. Human carbonic anhydrase II-IN-1 can be used for glaucoma research.

Carbonic anhydrase inhibitor 9 is a potent inhibitor of carbonic anhydrase (CA) that acts on hCA II (Ki: 56.4 nM) and IX (Ki: 56.9 nM) and exhibits antiproliferative effects.

Carbonic anhydrase inhibitor 11 (compound VI) is a potent, selective carbonic anhydrase inhibitor that acts on CA II (Ki: 40 nM), CA IX (Ki: 39 nM) and CA XII (Ki: 900 nM).

Carbonic anhydrase inhibitor 14 (Compound 8b) is a potent CA inhibitor, exhibiting K i values of 1203, 99.7, 9.4, and 27.7 nM against hCA I, hCA II, hCA IX, and hCA XII, respectively. Additionally, it effectively inhibits CDK2 with an IC 50 of 20.3 μM. Furthermore, Carbonic anhydrase inhibitor 14 demonstrates significant antitumor activity [1].

Carbonic anhydrase inhibitor 4 is a photoprobe that inhibits the activity of carbonic anhydrase. It specifically targets human carbonic anhydrases, including hCA I-XIV, with K i values ranging from 640-1166 nM [1].

Carbonic anhydrase inhibitor 3 (compound 11g) is an inhibitor of carbonic anhydrase II that reduces the intraocular pressure in glaucomatous rabbits [1].

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].

Carbonic anhydrase inhibitor 13 (compound 7) is a potent inhibitor of carbonic anhydrase (CA).

Carbonic anhydrase inhibitor 10 can be used in the research of cancer that shows anti-proliferative activity against MCF-7 cancer cell line with an IC50 of 11.9 μM. Carbonic anhydrase inhibitor 10 is a potent inhibitor of h CA IX with a Ki value of 6.2 nM [1].

Carbonic anhydrase inhibitor 5 is a potent and selective inhibitor of human carbonic anhydrase (hCA), acting on hCA II (IC50: 42.9 nM), hCA IX (IC50: 47.6 nM) and hCA XII (IC50: 6.7 nM).

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.

JNJ-26990990 is a broad-spectrum anticonvulsant drug as a second-generation followup to the marketed drug topiramate. It was designed to have the same anticonvulsant effects as topiramate, but without the side effects associated with topiramate's carbonic

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.

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.

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

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.

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.

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

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

Mafenide acetate, a sulfonamide, inhibits the enzyme carbonic anhydrase and is used as a topical anti-infective drug, especially in burn therapy.

Zonisamide-13C2,15N is intended for use as an internal standard for the quantification of zonisamide by GC- or LC-MS. Zonisamide is an antiepileptic agent.1 It selectively inhibits the repeated firing of sodium channels (IC50 = 2 μg/ml) in mouse embryo spinal cord neurons and inhibits spontaneous channel firing when used at concentrations greater than 10 μg/ml.2 In rat cerebral cortex neurons, zonisamide (1-1,000 μM) inhibits T-type calcium channels with a maximum reduction of 60% of the calcium current.3 Zonisamide inhibits H. pylori recombinant carbonic anhydrase (CA) and the human CA isoforms I, II, and V with Ki values of 218, 56, 35, and 21 nM, respectively.4,5 In mice, it has anticonvulsant activity against maximal electroshock seizure (MES) and pentylenetetrazole-induced maximal, but not minimal, seizures (ED50s = 19.6, 9.3, and >500 mg/kg, respectively). Zonisamide (40 mg/kg, p.o.) prevents MPTP-induced decreases in the levels of dopamine , but not homovanillic acid or dihydroxyphenyl acetic acid , and increases MPTP-induced decreases in the dopamine turnover rate in mouse striatum in a model of Parkinson's disease.6 Formulations containing zonisamide have been used in the treatment of partial seizures in adults with epilepsy. |1. Masuda, Y., Ishizaki, M., and Shimizu, M. Zonisamide: Pharmacology and clinical efficacy in epilepsy. CNS Drug Rev. 4(4), 341-360 (1998).|2. Rock, D.M., Macdonald, R.L., and Taylor, C.P. Blockade of sustained repetitive action potentials in cultured spinal cord neurons by zonisamide (AD 810, CI 912), a novel anticonvulsant. Epilepsy Res. 3(2), 138-143 (1989).|3. Suzuki, S., Kawakami, K., Nishimura, S., et al. Zonisamide blocks T-type calcium channel in cultured neurons of rat cerebral cortex. Epilepsy Res. 12(1), 21-27 (1992).|4. Nishimori, I., Vullo, D., Minakuchi, T., et al. Carbonic anhydrase inhibitors: Cloning and sulfonamide inhibition studies of a carboxyterminal truncated α-carbonic anhydrase from Helicobacter pylori. Bioorg. Med. Chem. Lett. 16(8), 2182-2188 (2006).|5. De Simone, G., Di Fiore, A., Menchise, V., et al. Carbonic anhydrase inhibitors. Zonisamide is an effective inhibitor of the cytosolic isozyme II and mitochondrial isozyme V: Solution and X-ray crystallographic studies. Bioorg. Med. Chem. Lett. 15(9), 2315-2320 (2005).|6. Yabe, H., Choudhury, M.E., Kubo, M., et al. Zonisamide increases dopamine turnover in the striatum of mice and common marmosets treated with MPTP. J. Pharmacol. Sci. 110(1), 64-68 (2009).

ETHYL 3,5-DIHYDROXYBENZOATE is a natural product. It inhibits human carbonic anhydrase 2.

Chlorthalidone impurity G is a potential impurity found in commercial preparations of chlorthalidone that has moderate antihypertensive effects. Chlorthalidone is a thiazide-like diuretic that inhibits the Na+/Cl- cotransporter in the distal convoluted tubule of the kidney, which prevents reabsorption of sodium and chloride leading to a reduction in plasma volume and cardiac output. It also inhibits carbonic anhydrase (CA), including the isoforms CAVB, VII, IX, XII, and XIII (Kis = 2.8-23 nM) and, to a lesser extent, CAI, CAII, IV, VA, and VI (Kis = 138-1,347 nM), which may mediate its sustained vasodilatory activity. Dietary administration of chlorthalidone (8 mg per animal per day) reduces arterial hypertension and prevents or reduces ventricular hypertrophy induced by deoxycorticosterone acetate (DOCA) in salt-hypertensive rats. Formulations containing chlorthalidone have been used alone or in combination with other antihypertensive agents to lower arterial blood pressure and as adjuvants to address edema caused by cardiac or renal disorders.

Pomiferin is a natural product inhibitor of carbonic anhydrase I and II isoenzymes. It has anticancer, antibacterial and antidiabetic properties. Pomiferin has anti-inflammatory and neuroprotective activities.

Dichlorphenamide-13C6is intended for use as an internal standard for the quantification of dichlorphenamide by GC- or LC-MS. Dichlorphenamide is a sulfonamide and an orally bioavailable carbonic anhydrase (CA) inhibitor (Kis = 1.20, 38, 50, and 50 nM for the human CA isoforms CAI, CAII, CAIX, and CAXII, respectively).1It lowers intraocular pressure in rabbits when 50 μl of a 10% solution is applied topically to the eye.2Dichlorphenamide rescues the potassium deficiency and prevents insulin-induced paralysis in a rat model of familial hypokalemic periodic paralysis when administered at a dose of 5.6 mg/kg per day for ten days.3Formulations containing dichlorphenamide have been used in the treatment of glaucoma and primary periodic paralysis.

Dorzolamide is an anti-glaucoma agent and is a carbonic anhydrase inhibitor.

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

Topiramate lithium (McN 4853) is a wide-ranging antiepileptic compound with GluR5 receptor antagonistic properties. Its mechanism of action involves enhancing GABAergic activity, inhibiting kainate/AMPA receptors, voltage-sensitive sodium and calcium channels, and increasing potassium conductance. Additionally, this compound inhibits carbonic anhydrase. [1][2][3]

VM4-037 is a PET imaging agent used for carbonic anhydrase IX.

Sezolamide hydrochloride is a potent topical carbonic anhydrase inhibitor.

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].

L-693612 HCl is an inhibitor of carbonic anhydrase.

CAII-IN-1 (compound 3n) is a thiosemicarbazide derivative that acts as a potent and selective inhibitor of carbonic anhydrase-II (CA-II), with an IC50 value of 10.3 μM for bovine CA-II. This compound (CAII-IN-1) finds utility in research pertaining to carbonic anhydrase-associated biological disorders [1].

(+)-Xylariamide A is a probe used for mycobacterial and fungal carbonic anhydrase.