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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Carbonic anhydrase-IN-35
0 ImagesCat. No.: HY-175638Carbonic anhydrase-IN-35 is a selective carbonic anhydrase (CA) inhibitor. Carbonic anhydrase-IN-35 potently inhibits tumor-associated hCA IX (Ki = 0.6 nM) and hCA XII (Ki = 2.2 nM). Carbonic anhydrase-IN-35 induces apoptosis in MCF-7 cells by elevating Bax, reducing Bcl-2, and downregulating CDK4/6. Carbonic anhydrase-IN-35 exhibits potent cytotoxicity against MCF-7 (IC50 = 0.3975 μM normoxic/0.6575 μM hypoxic), MCF-7-ADR (IC50> = 0.3975 μM normoxic/4.488 μM hypoxic), MDA-MB-231, and 4T1 breast cancer cells. Carbonic anhydrase-IN-35 can be used for the study of breast cancer.
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hCAIX-IN-21
0 ImagesCat. No.: HY-159128CAS No.: 3047757-55-8hCAIX-IN-21 (compound 16c) is a potent hCAIX inhibitor with KI values of 5.2, 3.5, 12.6, 13600 nM for hCAIX, hCA II, hCA XII, hCA I, respectively. hCAIX-IN-21 inhibits cathepsin B enzyme activity.
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STAT3/CAIX-IN-1
0 ImagesCat. No.: HY-174457CAS No.: 3053583-60-8STAT3/CAIX-IN-1 is a dual-target inhibitor of STAT3 (Kd: 60.03 μM) and CAIX (IC50: 80.45 nM). STAT3/CAIX-IN-1 induces ferroptosis by increases the levels of reactive oxygen species (ROS) and lipid peroxides. STAT3/CAIX-IN-1 inhibits cell migration, induces apoptosis, and causes cell cycle arrest in MDA-MB-231 cells. STAT3/CAIX-IN-1 can be used for the study of triple-negative breast cancer (TNBC).
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CAII-IN-11
0 ImagesCat. No.: HY-180916CAII-IN-11 (Compound A1) is a dual-target compound that contains a hCA II inhibitor (IC₅₀ = 2 nM) portion and a NO donor portion. CAII-IN-11 also has inhibitory activity against hCA IX, hCA XII, and hCA I, with IC50 values of 6, 3, and 152 nM respectively. CAII-IN-11 significantly increases the intracellular cGMP level in human trabecular meshwork cells. CAII-IN-11 reduces the apoptosis of retinal ganglion cells by reducing oxidative stress (ROS levels), inhibiting astrocytes and the NLRP3 inflammasome activation. CAII-IN-11 has hypotensive activity in rabbit models and can be used for the study of glaucoma.
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hCAIX-IN-10
0 ImagesCat. No.: HY-147827CAS No.: 2497504-72-8hCAIX-IN-10 (Compound 6i) is a selective carbonic anhydrase IX and XII inhibitor with Ki s of 61.5 and 586.8 nM for hCA IX and hCA XII, respectively. hCA IX and hCA XII are transmembrane isoforms which have been characterized as biomarkers for several types of tumors. The hCA XII assists in maintenance of acid-base homoeostasis in normal as well as tumor cells.
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hCAII-IN-3
0 ImagesCat. No.: HY-146008CAS No.: 2770927-76-7hCAII-IN-3 (Compound 16) is a human carbonic anhydrase (hCA) inhibitor with Ki values of 403.8, 5.1, 10.2 and 5.2 nM against hCA I, hCA II, hCA IX and hCA XII, respectively. hCA IX-IN-2 shows anticancer activity.
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hCAIX-IN-23
0 ImagesCat. No.: HY-168030hCAIX-IN-23 (Compound 27) is a human carbonic anhydrase (hCA) inhibitor with Ki values of 10.4 and 8.5 nM for hCA IX and hCA XII, respectively. In addition to inhibiting hCA activity, hCAIX-IN-23 releases NO, exhibiting dual antitumor activity. hCAIX-IN-23 induces apoptosis by regulating mitochondrial caspase activity and the ferroptosis pathway (ferroptosis) through the downregulation of hCA IX and iron-regulatory protein expression. hCAIX-IN-23 is useful for renal cancer research.
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hCAIX/XII-IN-15
0 ImagesCat. No.: HY-173394CAS No.: 69141-46-4hCAIX/XII-IN-15 (Compound 17β) is an inhibitor of hCA IX and hCA XII, with Kis of 0.42 and 4.37 μM respectively. hCAIX/XII-IN-15 has pro-apoptotic effect in multiple myeloma cells.
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hCAIX/XII-IN-9
0 ImagesCat. No.: HY-162063hCAIX/XII-IN-9 (compound 8) is a potent carbonic anhydrase (CA) inhibitor with Ki values of 1658 nM, 184.8 nM, 8.9 nM, 64.8 nM for hCA I, hCA II, hCA IX, and hCA XII, respectively.
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ALP/Carbonic anhydrase-IN-1
0 ImagesALP/Carbonic anhydrase-IN-1 (Compound 1e) is a dual carbonic anhydrase (CA) and alkaline phosphatase (ALP) inhibitor. ALP/Carbonic anhydrase-IN-1 shows IC50 values of 0.44 µM, 1.61 µM, 0.51 µM, and 0.107 µM for CA-II, CA-IX, CA-XII, and ALP, respectively.
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CAIX-IN-18
0 ImagesCat. No.: HY-184789CAIX-IN-18 is a competitive carbonic anhydrase IX (CA IX) inhibitor with a Ki value of 1.76 μM. CAIX-IN-18 can be used for the research of colorectal cancer.
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CAIX/XII-IN-18
0 ImagesCat. No.: HY-183591CAIX/XII-IN-18 is a selective human carbonic anhydrase IX/XII (CA IX/XII) inhibitor with Ki values of 28.1 nM (hCA IX) and 11.6 nM (hCA XII). CAIX/XII-IN-18 induces apoptosis in breast cancer cells. CAIX/XII-IN-18 can be used for the research of breast cancer, pancreatic cancer.
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HCAIX-IN-1
0 ImagesCat. No.: HY-146206CAS No.: 2389034-65-3HCAIX-IN-1 is a selective HCAIX inhibitor with a Ki value of 3.3 nM for hCA IX. HCAIX-IN-1 can be used in the study of solid tumors.
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Carbonic anhydrase inhibitor 20
0 ImagesCat. No.: HY-161374CAS No.: 3034045-43-4Carbonic anhydrase inhibitor 20 (compound 11) is an inhibitor of piperazinosulfonamide carbonic anhydrase (Carbonic Anhydrase). The Ki of Carbonic anhydrase inhibitor 20 for hCA I, hCA II, hCA IX, and hCA XII are 47.6 nM, 36.5 nM, 8.3 nM, and 2.7 nM respectively.
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Carbonic anhydrase-IN-34
0 ImagesCat. No.: HY-175315Carbonic anhydrase-IN-34 is a carbonic anhydrases (CAs) inhibitor (compound 9d) with IC50s of 1.01 μM against hCA-II, 0.21 μM against hCA-IX and 0.88 μM against hCA-XII. Carbonic anhydrase-IN-34 has potential applications in the research of several disorders, including epilepsy, glaucoma, obesity, and cancer.
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hCAIX-IN-12
0 ImagesCat. No.: HY-146254CAS No.: 2414598-85-7hCAIX-IN-12 is a potent hCAIX inhibitor with IC50 values of 0.74, 10.78 μM for CAIX and CAII, respectively. hCAIX-IN-12 shows antiproliferative effect and induces apoptosis. hCAIX-IN-12 increases ROS production. hCAIX-IN-12 has the potential for the research of colorectal cancer (CRC) .
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hCAIX/XII-IN-1
0 ImagesCat. No.: HY-146988CAS No.: 3033040-76-2hCAIX/XII-IN-1 is a potent CAIX/XII inhibitor with the KI values of 0.48 µM and 0.83 µM for CAIX and CAXII, respectively. hCAIX/XII-IN-1 shows antiproliferative activity in vitro. hCAIX/XII-IN-1 induces apoptosis in MCF-7 cells.
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hCAIX-IN-8
0 ImagesCat. No.: HY-147722CAS No.: 2414633-40-0hCAIX-IN-8 (compound 7i) is a potent and selective hCAIX inhibitor with IC50s of 1.99, 0.024, 1.10 μM for CAII, CAIX, CAVA respectively. hCAIX-IN-8 shows anti-proliferation activity with low toxicity. hCAIX-IN-8 decreases the epithelial to mesenchymal transitions and induces apoptosis. hCAIX-IN-8 inhibits cell migration and colonization potential.
