CA IX
Carbonic anhydrase IX (CA IX, CA9) is a transmembrane, tumor-associated carbonic anhydrase isoform that catalyzes the reversible hydration of carbon dioxide to bicarbonate and protons, thereby contributing to cellular and extracellular pH regulation under hypoxic conditions[1][2]. CA IX is strongly induced by hypoxia through hypoxia-inducible factor (HIF)-dependent transcriptional regulation and functions as a key component of the adaptive response of tumor cells to oxygen deprivation[3][4]. Mechanistically, CA IX supports the bicarbonate import arm of pH-control machinery and participates directly in the establishment of an acidic tumor microenvironment while maintaining conditions compatible with cancer cell survival and proliferation[1][5][6]. Consequently, CA IX contributes to extracellular acidification, tumor progression, invasion, metastasis, and resistance to therapy in multiple solid tumors[5][7][8]. In disease models, CA IX expression is broadly associated with hypoxic regions of tumors and has been linked to poor prognosis, increased metastatic potential, and aggressive tumor phenotypes[7][8][9]. Compared with related carbonic anhydrase isoforms, CA IX possesses a unique extracellular proteoglycan domain that is absent from other family members and is considered a distinctive structural feature relevant to its biological functions in the tumor microenvironment[2]. Furthermore, CA IX is one of only a few carbonic anhydrase isoenzymes with strong tumor association and limited expression in most normal tissues, enhancing its value as a disease biomarker and experimental target[10][11]. For research applications, selective sulfonamide-based CA IX inhibitors suppress CA IX-mediated extracellular acidification and have been widely employed for functional studies, molecular imaging, and evaluation of therapeutic strategies targeting hypoxic tumors[6][12].
References:
- [1]. Sedlakova O, et al. Carbonic anhydrase IX, a hypoxia-induced catalytic component of the pH regulating machinery in tumors. Front Physiol. 2014 Jan 8;4:400. [Content Brief]
- [2]. Venkateswaran G, et al. Interplay of Carbonic Anhydrase IX With Amino Acid and Acid/Base Transporters in the Hypoxic Tumor Microenvironment. Front Cell Dev Biol. 2020;8:602668.
- [3]. Wykoff CC, et al. Hypoxia-inducible expression of tumor-associated carbonic anhydrases. Cancer Res. 2000;60(24):7075-7083.
- [4]. Pastorekova S, et al. Molecular mechanisms of carbonic anhydrase IX-mediated pH regulation under hypoxia. BJU Int. 2008 Jun;101 Suppl 4:8-15. [Content Brief]
- [5]. Lee SH, et al. Carbonic anhydrase IX is a pH-stat that sets an acidic tumour extracellular pH in vivo. Br J Cancer. 2018;119:622-630.
- [6]. Svastová E, et al. Hypoxia activates the capacity of tumor-associated carbonic anhydrase IX to acidify extracellular pH. FEBS Lett. 2004 Nov 19;577(3):439-45. [Content Brief]
- [7]. Aldera AP, et al. Carbonic anhydrase IX: a regulator of pH and participant in carcinogenesis. J Clin Pathol. 2021;74(6):350-354.
- [8]. Pastorekova S, et al. The role of carbonic anhydrase IX in cancer development: links to hypoxia, acidosis, and beyond. Cancer Metastasis Rev. 2019;38:65-77.
- [9]. Chafe SC, et al. Targeting Hypoxia-Induced Carbonic Anhydrase IX Enhances Immune-Checkpoint Blockade Locally and Systemically. Cancer Immunol Res. 2019;7(7):1064-1078.
- [10]. CA IX gene information from NCBI.
- [11]. Cecchi A, et al. Carbonic anhydrase inhibitors. Design of fluorescent sulfonamides as probes of tumor-associated carbonic anhydrase IX that inhibit isozyme IX-mediated acidification of hypoxic tumors. J Med Chem. 2005 Jul 28;48(15):4834-41. [Content Brief]
- [12]. Bao B, et al. In vivo imaging and quantification of carbonic anhydrase IX expression as an endogenous biomarker of tumor hypoxia. PLoS One. 2012;7(11):e50860. [Content Brief]
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CA IX Related Products (102)
Related Products (102)
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Recombinant Proteins (3)
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Acetazolamide
0 ImagesAcetazolamide is a carbonic anhydrase (CA) IX inhibitor with an IC50 of 30 nM for hCA IX. Acetazolamide has diuretic, antihypertensive and anti-gonococcal activities.
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U-104
0 ImagesSynonyms: SLC-0111U-104 (SLC-0111) is a potent carbonic anhydrase (CA) inhibitor for CA IX and CA XII with Ki values of 45.1 nM and 4.5 nM, respectively. U-104 shows a significant delay in tumor growth in mice model.
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Girentuximab
0 ImagesSynonyms: G250; cG250Girentuximab (G250) is a chimeric monoclonal antibody that binds carbonic anhydrase IX (CAIX), a cell surface glycoprotein ubiquitously expressed in clear cell renal cell carcinoma (ccRCC).
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Acetazolamide sodium
0 ImagesAcetazolamide sodium is a carbonic anhydrase (CA) IX inhibitor with an IC50 of 30 nM for hCA IX. Acetazolamide sodium has diuretic, antihypertensive and anti-gonococcal activities.
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DPI-4452
0 ImagesDPI-4452 is a CAIX-targeting cyclic peptide with a DOTA cage, and can be chelated with radionuclide for CAIX-expressing tumor PET-CT imaging and study. DPI-4452 specifically and selectively binds CAIX without interaction with an in vitro off-target receptor panel of 55 targets (IC50 for recombinant hCAIX: 130 nM). Radiolabeled DPI-4452 inhibits tumor growth in HT-29 and SK-RC-52 xenograft mouse models. DPI-4452 can be used for the synthesis/research of Radionuclide-Drug Conjugates (RDCs).
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BAY-79-4620 Antibody
0 ImagesCat. No.: HY-P992322BAY-79-4620 Antibody is a potent and selective CAIX antibody with a human CAIX Kd of 3.6 nM. BAY-79-4620 Antibody yields antibody-drug conjugate (ADC) through conjugating with Monomethyl auristatin E (HY-15162) via a self-immolative enzyme-cleavable linker. BAY-79-4620 Antibody can be used for the research of cervical carcinoma, non-small cell lung carcinoma, breast carcinoma, pancreatic carcinoma, gastric carcinoma, prostate carcinoma.
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COX-2-IN-67
0 ImagesCat. No.: HY-184292COX-2-IN-67 is an orally active, blood-brain barrier permeable multi-target inhibitor that potently targets COX-2 (IC50=0.07 μM), hCA IX (Ki=62.7 nM) and hBuChE (IC50=0.47 μM). COX-2-IN-67 alleviates oxidative stress and liver stress, improves glucose homeostasis and insulin sensitivity, and optimizes lipid profiles. Meanwhile, COX-2-IN-67 effectively reduces the levels of neuroinflammatory markers and improves hippocampus-dependent cognitive function in a high-fat diet-induced rat model. COX-2-IN-67 can be used for the research of metabolic dysfunction-associated mild cognitive impairment.
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CA/PRAK-IN-1
0 ImagesCat. No.: HY-184792CA/PRAK-IN-1 is a dual inhibitor of carbonic anhydrase (Carbonic Anhydrase) and PRAK, with a Ki of 20.1 nM against hCA IX and 16.4 nM against hCA XII. CA/PRAK-IN-1 exhibits inhibitory activity against YES1 kinase, BTK, and MAP4K3. CA/PRAK-IN-1 induces G0/G1 phase arrest of the cancer cell cycle, inhibits DNA synthesis, disrupts hypoxia-driven survival pathways, promotes cell death, and shows broad-spectrum cytotoxicity against tumor cells. CA/PRAK-IN-1 can be used in research on various cancers including leukemia, colon cancer, melanoma, and renal cancer.
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Acetazolamide (Standard)
0 ImagesAcetazolamide (Standard) is the analytical standard of Acetazolamide. This product is intended for research and analytical applications. Acetazolamide is a carbonic anhydrase (CA) IX inhibitor with an IC50 of 30 nM for hCA IX. Acetazolamide has diuretic, antihypertensive and anti-gonococcal activities.
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CAIX Inhibitor S4
0 ImagesCAIX Inhibitor S4 is a potent and selective inhibitor of carbonic anhydrase IX/XII (CA IX/XII), with a Ki of 7 nM and 2 nM, respectively. CAIX Inhibitor S4 also inhibits CA II and CA I (Ki=546 and 5600 nM, respectively). CAIX Inhibitor S4 can inhibit the number of lung metastasis in orthotopic MDA-MB-231 mouse model without affecting primary tumor growth.
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5,6-Dihydro-2H-pyran-2-one
0 ImagesCat. No.: HY-W044762CAS No.: 3393-45-15,6-Dihydro-2H-pyran-2-one (Compound 1) is a prodrug-type carbonic anhydrase inhibitor. 5,6-Dihydro-2H-pyran-2-one can specifically inhibit the tumor-associated subtype hCA IX and the cytoplasmic subtype hCA I with Ki values of 1.35 and 8.03 μM. 5,6-Dihydro-2H-pyran-2-one can be used for the research on hypoxia-related cancer.
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Furagin
0 ImagesFuragin (Furazidine), an analogue of Nitrofurantoin (HY-A0090), is an antibiotic with antibacterial activity against ESKAPE pathogens with MIC values of 0-32 µg/mL. Furagin inhibits human Carbonic anhydrases . Furagin is promising for research of cancer and urinary tract infections (UTIs).
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Elsulfavirine
0 ImagesSynonyms: R-1206Elsulfavirine (R-1206) is an orally active human carbonic anhydrase (carbonic anhydrase, CA) inhibitor and an allosteric inhibitor of HIV-1 non-nucleoside reverse transcriptase (NNRT). Elsulfavirine also targets and blocks the interaction between adenylosuccinate lyase (ADSL) and insulin-induced gene proteins INSIG1/2, blocks SREBP-1-mediated de novo lipid synthesis, and inhibits the proliferation of liver cancer cells. The combination of Elsulfavirine and Lenvatinib (HY-10981) produces a synergistic anti-tumor effect. Elsulfavirine is converted into the active metabolite VM1500A in vivo, blocks the DNA polymerase activity of reverse transcriptase, and inhibits HIV-1 replication. Elsulfavirine exhibits a Ki of 1960 nM-52400 nM against human carbonic anhydrase isoforms including I, VII, VI, VA, VB, IX, XIII, XIV. Elsulfavirine is used in studies related to HIV-1 infection and liver cancer.
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2-Aminobenzenesulfonamide
0 Images2-Aminobenzenesulfonamide is a carbonic anhydrase IX inhibitor.
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4-Chloro-3-sulfamoylbenzoic acid
0 Images4-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.
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Lasamide
0 ImagesLasamide is a potent human Carbonic Anhydrase inhibitor with Ki values of 7.54 and 2.76 nM for hCAXII and hCAIX, respectively.
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Enpp/Carbonic anhydrase-IN-2
0 ImagesEnpp/Carbonic anhydrase-IN-2 (compound 1i) is a potent Enpp and carbonic anhydrase inhibitor with IC50s 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.
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hCAVII/IX-IN-1
0 ImageshCAVII/IX-IN-1 (compound 4) is a hCAVII/IX inhibitor, with Ki values of 56.5 nM and 38.2 nM, respectively. hCAVII/IX-IN-1 can be used in anticancer research.
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hCAIX-IN-18
0 ImageshCAIX-IN-18 (compound 30) is an inhibitor of carbonic anhydrase (CA), with Kis 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.
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GZ22-4
0 ImagesCat. No.: HY-D2345Purity: 99.37%GZ22-4 is a near-infrared (NIR) fluorescent probe. GZ22-4 shows high affinity for carbonic anhydrase IX (CAIX), with a Kd of 0.2 nM. GZ22-4 can be used for the research of visualize CAIX-positive tumors.
