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 (106)
Related Products (106)
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Recombinant Proteins (3)
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BAY-79-4620 Antibody
0 ImagesCat. No.: HY-P992322Purity: 99.9%BAY-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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Acetazolamide-13C2,d3
0 ImagesCat. No.: HY-B0782S1Acetazolamide-13C2,d3 is the 13C- and deuterium labeled Acetazolamide. Acetazolamide is a carbonic anhydrase (CA) IX inhibitor with an IC50 of 30 nM for hCA IX. Diuretic effects.
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EGFR/CA-IX-IN-1
0 ImagesCat. No.: HY-174232EGFR/CA-IX-IN-1 (Compound 14) is a dual inhibitor against epidermal growth factor receptor (EGFR) and carbonic anhydrase IX (CA-IX) with IC50 values of 5.92 nM and 63 nM, respectively. EGFR/CA-IX-IN-1 shows strong cytotoxicity against breast cancer cells (MDA-MB-231, MCF-7) with IC50 values of 5.78 μM and 8.05 μM, respectively. EGFR/CA-IX-IN-1 inhibits the catalytic activity of CA-IX, up-regulates BAX/Bcl-2, activates caspases, and arrests the cell cycle at the G1 phase. EGFR/CA-IX-IN-1 is promising for research of breast cancer.
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hCAIX/XII-IN-5
0 ImagesCat. No.: HY-150695CAS No.: 2421127-99-1hCAIX/XII-IN-5 (Coumarin 9a) a carbonic anhydrase (CA) inhibitor, and exhibits excellent hCA IX/XII selectivity (Ki=93.9 and 85.7 nM, respectively) over hCA I and hCA II. hCAIX/XII-IN-5 shows anti-proliferative activities to cancer cells. hCAIX/XII-IN-5 can delay cell cycle and induce apoptosis.
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CAXII-IN-3
0 ImagesCat. No.: HY-178030CAXII-IN-3 is an effective carbonic anhydrase (CA XII) inhibitor with a Ki of 53 nM. CAXII-IN-3 exhibits selective inhibition against multiple human CA subtypes with Kis of 5.3 μM, 75 nM, 1.9 μM, > 10 μM against CA I, CA II, CA IV and CA IX. CAXII-IN-3 mainly inhibits CA II and XII, and reduces aqueous humor production. CAXII-IN-3 exhibits β3-AR agonistic activity, can dilate retinal blood vessels, and improve optic nerve perfusion. CAXII-IN-3 can be used in the research of ocular disorders such as glaucoma.
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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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α-Glucosidase-IN-63
0 ImagesCat. No.: HY-161522CAS No.: 2375866-82-1α-Glucosidase-IN-63 (Compound 4d) is an inhibitor of α-Glucosidase (IC50=0.44 μM). α-Glucosidase-IN-63 inhibits hCA II with an activity of Ki= 7.0 nM. α-Glucosidase-IN-63 is orally effective..
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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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hCAIX/XII-IN-6
0 ImagesCat. No.: HY-151472CAS No.: 3031666-31-3hCAIX/XII-IN-6 is an orally active carbonic anhydrase (CA) inhibitor. hCAIX/XII-IN-6 inhibits human CA isoforms hCA I, II, IV, IX, and XII with Ki values of 6697 nM, 2950 nM, 4093 nM, 4.1 nM and 7.7 nM, respectively. hCAIX/XII-IN-6 can be used for the research of rheumatoid arthritis (RA).
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CAIX/XII-IN-17
0 ImagesCat. No.: HY-183590CAIX/XII-IN-17 is a selective human carbonic anhydrase IX/XII (CA IX/XII) inhibitor with Ki values of 25.1 nM (hCA IX) and 35.2 nM (hCA XII). CAIX/XII-IN-17 induces apoptosis in pancreatic cancer cells. CAIX/XII-IN-17 can be used for the research of breast cancer, pancreatic cancer.
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hCAII-IN-9
0 ImageshCAII-IN-9 is a potent carbonic anhydrase inhibitor with IC50s of 1.18 μM (hCA II), 0.17 μM (hCA IX), and 2.99 μM (hCA XII), respectively. hCAII-IN-9 has no blood-brain barrier permeability.
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hCA-IN-1
0 ImagesCat. No.: HY-175245hCA-IN-1 (Compound 5u) is an hCA inhibitor with Ki values of 159.2, 4.8, 15.5, and 2 nM against hCA I, hCA II, hCA IX, and hCA XII, respectively. hCA-IN-1 exhibits broad-spectrum anticancer activity against melanoma, breast, and colon cancer cells. ADME predictions indicate that hCA-IN-1 has good solubility and oral bioavailability. hCA-IN-1 can be used in tumor research.
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hCAXII-IN-1
0 ImagesCat. No.: HY-147664CAS No.: 2451479-66-4These compounds show selective inhibition on tumor related subtypes HCA IX and XII, and are also considered as the leading molecules for the development of future cancer therapeutic drugs based on new mechanisms of action.
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hCAIX/XII-IN-11
0 ImagesCat. No.: HY-163414hCAIX/XII-IN-11 (Compound 6c) is an inhibitor of hCA IX and hCA XII with a Ki value of 0.7 μM for both the isoforms. hCAIX/XII-IN-11 can be used for anticancer research.
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Carbonic anhydrase inhibitor 14
0 ImagesCat. No.: HY-150570CAS No.: 2410402-75-2Carbonic anhydrase inhibitor 14 (Compound 8b) is a carbonic anhydrase (CA) inhibitor with Ki values of 1203, 99.7, 9.4 and 27.7 nM against hCA I, hCA II, hCA IX and hCA XII, respectively. Carbonic anhydrase inhibitor 14 can also inhibit CDK2 with an IC50 of 20.3 μM. Carbonic anhydrase inhibitor 14 shows antitumor activity.
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CAII-IN-15
0 ImagesCat. No.: HY-183283CAII-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.
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Carbonic anhydrase-IN-37
0 ImagesCat. No.: HY-180189Carbonic anhydrase-IN-37 (compound 9a) is a potent and orally active carbonic anhydrase (CA) inhibitor with Kis of 9.7 and 1.0 nM for hCA VA and hCA VB, respectively. Carbonic anhydrase-IN-37 shows anti allodynic and antihyperalgesic effects on Paclitaxel (HY-B0015)-induced neuropathic pain in mice. Carbonic anhydrase-IN-37 can be used for neuropathic pain research.
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CAIX/XII/NAMPT-IN-1
0 ImagesCat. No.: HY-181350CAIX/XII/NAMPT-IN-1 is a triple inhibitor of carbonic anhydrase IX/XII and nicotinamide phosphoribosyltransferase (NAMPT) with a hCA IX Ki of 78.1 nM, hCA XII Ki of 64.4 nM, and hNAMPT IC50 of 168 nM. CAIX/XII/NAMPT-IN-1 induces apoptosis, ROS accumulation, suppresses ERK/AKT signaling, inhibits DNA synthesis, and causes mitochondrial dysfunction. CAIX/XII/NAMPT-IN-1 exerts antiproliferative effects against multiple cancer cells under normoxic and hypoxic conditions. CAIX/XII/NAMPT-IN-1 can be used for the research of cancer, such as renal carcinoma, glioblastoma and colorectal cancer.
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CAIX/CAXII-IN-1
0 ImagesCat. No.: HY-146819CAS No.: 2439165-37-2Compound 9 is the most effective against tumor specific Ca ix/ca XII (ki=29.1 and 8.8 nm), so it is possible to evaluate its cytotoxicity and selectivity to HepG-2, HCT-116 and MCF-7 cancer cell lines in vitro, and its IC50 values to tumor cells are 1.78, 1.94 and 3.07, respectively μ M. It showed that it had obvious cytotoxicity.
