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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Thioaspirine
0 ImagesCat. No.: HY-44602CAS No.: 55819-78-8Thioaspirine is a carbonic anhydrase (CA) inhibitor with Kis of 64.3 and 10.9 μM for hCA II and hCA IX, respectively. Thioaspirine effectively relieves the inflammatory pain in CFA (HY-153808)-treated mice. Thioaspirine can be used for inflammatory pain research.
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VM4-037
0 ImagesCat. No.: HY-113719CAS No.: 1071470-72-8VM4-037 can be used for the synthesis of VM4-037(18F). VM4-037(18F) is a fluorinated PET imaging agent for carbonic anhydrase IX.
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DPP IV/hCA II-IN-1
0 ImagesCat. No.: HY-151578CAS No.: 2836996-95-1DPP IV/hCA II-IN-1 is a potent and selective dipeptidyl peptidase IV (DPP IV) and carbonic anhydrase (CA) inhibitor with an IC50 value of 0.049 μM for DPP IV and with Ki values of 0.0361, 0.0428, 0.0941, 0.1328, 0.2615, and 3.034 μM for CA II, CA VB, CA VA, CA IX, CA I, and CA IV, respectively.
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Anticancer agent 314
0 ImagesCat. No.: HY-182245Anticancer agent 314 is a multi-target anticancer agent with tubulin polymerization inhibitory activity (IC50 = 6.35 μM) and human carbonic anhydrase IX (Ki = 27.1 nM) and XII (Ki 20.9 = nM) inhibitory activity. Anticancer agent 314 binds to the colchicine-binding pocket of tubulin and inhibits tumor-associated carbonic anhydrase isoforms via zinc coordination within enzyme active sites. Anticancer agent 314 induces G2/M phase cell cycle arrest, apoptosis via p53-dependent signaling, and broad-spectrum antiproliferative activity across multiple cancer cells. Anticancer agent 314 can be used for the research of cancer, such as leukemia, melanoma, ovarian cancer.
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IPM-N001
0 ImagesCat. No.: HY-P11737IPM-N001 is a carbonic anhydrase IX (CAIX) ligand with a Kd value of <0.0337 nM for hCAIX. When radio-conjugated with 68Ga, IPM-N001 serves as a CAIX-targeted radionuclide tracer. [68Ga]Ga-IPM-N001 exhibits excellent tumor uptake and significantly improves the tumor-to-background ratio in PET/CT imaging studies using OS-RC-2 tumor-bearing mice. IPM-N001 can be used for the research of clear cell renal cell carcinoma.
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BE21349
0 ImagesCat. No.: HY-184660BE21349 is a carbonic anhydrase (CA) inhibitor with Ki values of 2090, 17.1, 61.8, and 40.5 nM against hCA I, hCA II, hCA IX, and hCA XII, respectively. BE21349 exhibits submicromolar inhibitory activity against leukemia, non-small cell lung cancer, and melanoma cell lines. BE21349 can be used in cancer-related research such as leukemia, non-small cell lung cancer, and melanoma.
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Carbonic anhydrase inhibitor 9
0 ImagesCat. No.: HY-144807CAS No.: 3033042-50-8Carbonic anhydrase inhibitor 9 is a potent carbonic anhydrase (CA) inhibitor with Kis of 56.4 and 56.9 nM for hCA II and IX, respectively. Antiproliferative activity.
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hCAIX-IN-15
0 ImagesCat. No.: HY-151632CAS No.: 2849348-43-0hCAIX-IN-15 is a potent hCA IX inhibitor with a Ki value of 38.8 nM. hCAIX-IN-15 shows good broad-spectrum anticancer activity and can be used for cancer research.
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CAIX/CAXII-IN-2
0 ImagesCat. No.: HY-159132CAS No.: 3067730-65-5CAIX/CAXII-IN-2 (compound 23) is a CAIX/CAXII inhibitor, with Ki values of 8.9 nM and 5.3 nM for CAIX/CAXII, respectively. CAIX/CAXII-IN-2 can be used in cancer research.
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CAIX/XII-IN-16
0 ImagesCat. No.: HY-179034CAIX/XII-IN-16 (Compound 5d) is a selective inhibitor of CA IX/XII and c-Met. CAIX/XII-IN-16‘s Ki values for hCA IX, hCA XII and CA I are 10.6, 31.8 and 2361 nM respectively, and its IC50 value for c-Met is 0.49 μM. CAIX/XII-IN-16 exhibits significantly enhanced cytotoxicity against colon cancer cells under hypoxic conditions. CAIX/XII-IN-16 causes cell cycle arrest and induces apoptosis (apoptosis). CAIX/XII-IN-16 significantly enhances the efficacy of Oxaliplatin (HY-17371) and 5-Fluorouracil (HY-90006). CAIX/XII-IN-16 can be used for studies on chemotherapy resistance related to hypoxia.
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HDAC-IN-91
0 ImagesCat. No.: HY-175021HDAC-IN-91 is a multiple inhibitor of HDAC (IC50 = 134.22 nM for HDAC1, 66.29 nM for HDAC2), carbonic anhydrase (CA) (Ki = 72.03 nM for CA IX, 50.76 nM for XII), and tubulin polymerization ( IC50 = 2.56 μM). HDAC-IN-91 inhibits PARP1 and increases the Bax/Bcl-2 ratio. HDAC-IN-91 blocks the cell cycle at the G2/M phase and induces apoptosis through a mitochondrial apoptosis activation mechanism. HDAC-IN-91 can exert potent cytotoxic activity through tubulin polymerization inhibition. HDAC-IN-91 can be used in breast, colorectal, cervical and lung cancer research.
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CAIX-IN-17
0 ImagesCat. No.: HY-181112CAIX-IN-17 is a carbonic anhydrase IX (CAIX) inhibitor with an IC50 of 61 nM and accumulates specifically in CAIX-expressing xenograft tumors. CAIX-IN-17 can be labeled with 68Ga and acts as a CAIX-targeted PET tracer for detection of clear-cell renal cell carcinoma.
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Carbonic anhydrase inhibitor 5
0 ImagesCat. No.: HY-144639CAS No.: 3033415-81-2Carbonic anhydrase inhibitor 5 is a potent and selective human carbonic anhydrase (hCA) inhibitor with IC50s of 42.9, 47,6 and 6.7 nM for hCA II, hCA IX and hCA XII, respectively.
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PDGFRA/CAIX/XII-IN-1
0 ImagesCat. No.: HY-181587Purity: 98.10%PDGFRA/CAIX/XII-IN-1 is an inhibitor of PDGFRA, CA IX and CA XII, with an IC50 of 20 nM against PDGFRA, a Ki of 93.3 nM against CA IX, and a Ki of 80.0 nM against CA XII. PDGFRA/CAIX/XII-IN-1 binds to the ATP-binding pocket of PDGFRA and blocks the downstream STAT3, AKT and ERK1/2 signaling pathways. PDGFRA/CAIX/XII-IN-1 induces G0/G1 cell cycle arrest and endogenous apoptosis (Apoptosis), including cleavage of PARP-1, caspase-9 and caspase-3, activation of caspase 3/7, and down-regulation of Mcl-1. PDGFRA/CAIX/XII-IN-1 exhibits antiproliferative activity in eosinophilic leukemia cells. PDGFRA/CAIX/XII-IN-1 can be used for the research of leukemia.
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CA IX/VEGFR-2-IN-2
0 ImagesCat. No.: HY-158328A
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CAIX-IN-4
0 ImagesCat. No.: HY-175223CAIX-IN-4 (Compound 8b) is a selective carbonic anhydrase IX (CAIX) inhibitor with an IC50 value of 0.32 μM. CAIX-IN-4 is promising for research of cancers such as renal cell carcinoma.
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NYM074
0 ImagesCat. No.: HY-183374NYM074 is a carbonic anhydrase IX (CAIX) ligand. NYM074 binds specifically to human CAIX to enable targeted radionuclide delivery. NYM074 supports dual radiolabeling with 68Ga for positron emission tomography (PET) imaging and 177Lu for radionuclide applications. NYM074 can be used for the research of clear cell renal cell carcinoma.
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CAXII-IN-4
0 ImagesCat. No.: HY-187173CAXII-IN-4 is a human carbonic anhydrase XII (hCA XII) inhibitor with Ki values of 4.9, 3079, 62.5 and 58.4 nM against hCA XII, hCA I, hCA II and hCA IX, respectively, showing high selectivity toward tumor-associated hCA XII. CAXII-IN-4 binds to the active site of hCA XII via a classic sulfamide binding mode, coordinates with Zn2+, forms a hydrogen bond with Ser133, and stabilizes the enzyme complex to reduce structural deviation. CAXII-IN-4 possesses both lipophilicity and polarity, and is predicted to have superior membrane permeability and oral absorbability. CAXII-IN-4 can be used in studies related to tumor-associated carbonic anhydrase inhibition.
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hCAIX/XII-IN-8
0 ImagesCat. No.: HY-156181CAS No.: 59994-64-8hCAIX/XII-IN-8 (compound 3g) is a potent human (carbonic anhydrase) CA IX and XII inhibitor, with Ki values of 8.5 and 6.7 nM, respectively. hCAIX/XII-IN-8 shows particularly strong inhibitory activity against the tumor-associated membrane-bound isoforms, hCA IX and XII, while maintaining a high selectivity ratio over cytosolic off-target isoforms hCA I and II.
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hCAIX/XII-IN-12
0 ImageshCAIX/XII-IN-12 (Compound 6) is a potent and highly selective dual inhibitor of hCA IX and hCA XII, with Ki values of 8.2 and 5.6 nM respectively. hCAIX/XII-IN-12 exhibits significant anti-proliferative activity against colon cancer cells, and this activity remains effective under hypoxic conditions. hCAIX/XII-IN-12 can be used for research on colon cancer.
