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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BCS12
0 ImagesBCS12 is a CAIX inhibitor. BCS12 inhibits the viability of cancer cells under hypoxic conditions. BCS12 elevates ROS levels and suppresses the expression of HIF-1α and CA9. BCS12 downregulates Bcl-2, activates caspase-9, caspase-3, caspase-7 and Bax, and induces PARP cleavage and apoptosis. BCS12 reduces tumor burden, increases the number of apoptotic nuclei and restores tissue structure in rats bearing breast tumors. BCS12 can be used in research related to triple-negative breast cancer.
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hCAIX-IN-24
0 ImagesCat. No.: HY-152001CAS No.: 3038222-64-6hCAIX-IN-24 is a potent and selectively hCA IX inhibitor with an KI value of 32.1 nM. hCAIX-IN-24 shows anti-proliferative activity.
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VEGFR/PDGFR/CA II-IN-1
0 ImagesCat. No.: HY-184656CAS No.: 3099422-14-4VEGFR/PDGFR/CA II-IN-1 is a VEGFR/PDGFR/CA II inhibitor. VEGFR/PDGFR/CA II-IN-1 potently inhibits VEGFR2 (IC50 = 62.66 nM), PDGFRα (IC50 = 18.65 nM), PDGFRβ (IC50 = 5.23 nM), and hCA II (Ki = 19.4 nM), with weaker activity against hCA I (Ki = 154.2 nM) and hCA IX (Ki = 121.0 nM). VEGFR/PDGFR/CA II-IN-1 exhibits potent antiproliferative activity in VEGFR2-BAF3 cells and robust inhibition of angiogenesis in human umbilical vein endothelial cells (HUVECs). VEGFR/PDGFR/CA II-IN-1 inhibits the formation of corneal neovascularization in rabbits through multiple signaling pathways, and significantly reduced intraocular pressure (IOP) in both acute and chronic glaucoma models. VEGFR/PDGFR/CA II-IN-1 can be used to study neovascular glaucoma (NVG).
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CAII-IN-14
0 ImagesCat. No.: HY-181510CAII-IN-14 (Compound 3o) is a human carbonic anhydrase II (hCA II) inhibitor with a Ki value of 1.65 nM. CAII-IN-14 also inhibits hCA I(Ki = 6.15 nM) and hCA IX(Ki = 5.43 nM). CAII-IN-14 exhibits predicted drug-like properties.
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hCAIX-IN-17
0 ImagesCat. No.: HY-146007hCA IX-IN-1 (Compound 6f) is a human carbonic anhydrase (hCA) inhibitor with Ki values of 331.4, 28.4, 9.4 and 17.8 nM against hCA I, hCA II, hCA IX and hCA XII, respectively. hCA IX-IN-1 shows anticancer activity.
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CA9hu-1
0 ImagesCat. No.: HY-P991887
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hCAIX-IN-14
0 ImagesCat. No.: HY-151633CAS No.: 77113-78-1hCAIX-IN-14 (compound 5a) is a potent inhibitor of human CA IX with a Ki value of 134.8 nM.
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Carbonic anhydrase inhibitor 10
0 ImagesCat. No.: HY-115994CAS No.: 2883453-30-1Carbonic anhydrase inhibitor 10 is a potent hCA IX inhibitor with a Ki value of 6.2 nM. Carbonic anhydrase inhibitor 10 exhibits anti-proliferative activity against MCF-7 cancer cell line with an IC50 of 11.9 μM. Carbonic anhydrase inhibitor 10 can be used for cancer research.
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hCA/VEGFR-2-IN-5
0 ImagesCat. No.: HY-163710hCA/VEGFR-2 IN-5 (compound 9) is an indolone-phenylsulfonamide and a potential dual inhibitor of cancer-related hCA IX/XII and VEGFR-2. The IC50 values of hCA/VEGFR-2-IN-5 for VEGFR-2, hCA IX and hCA XII are 0.38 μM, 40 and 3.2 nM, respectively. hCA/VEGFR-2-IN-5 has antitumor activity.
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COX-2-IN-30
0 ImagesCat. No.: HY-149269CAS No.: 1160498-08-7COX-2-IN-30 is a benzenesulfonamide derivative, as well as an orally active and dual inhibitor of COX (IC50=49 nM for COX-2, 10.4 μM for COX-1) and 5-LOX (IC50=2.4 μM). COX-2-IN-30 also inhibits transmembrane hCA IX and hCA XII isoform with nanomolar calss Ki values. COX-2-IN-30 exhibits analgesic, anti-inflammatory, and ulcerogenic activities, and does not show acute gastric effect.
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KCN1
0 ImagesCat. No.: HY-123009CAS No.: 927823-01-6KCN1 is a p300/HIF-1α interaction inhibitor with a Kd value of 345 nM for p300-CH1. KCN1 binds to the CH1 domain of p300, blocks the assembly of the p300/HIF-1α complex, and disrupts the HIF-1α-p300/CBP interaction. KCN1 inhibits cancer cell growth, induces cancer cell cycle arrest and apoptosis. KCN1 inhibits β-galactosidase activity and downregulates the expression of VEGF, Glut1, CA9 and CAIX. KCN1 exerts anticancer activity in mouse tumor xenograft models. KCN1 can be used in research related to malignant glioma, pancreatic cancer and metastatic uveal melanoma.
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CA IX-IN-2
0 ImagesCat. No.: HY-159122CAS No.: 3009842-92-3CA IX-IN-2 (Compound 9o) is an inhibitor for carbonic anhydrase (CA), that inhibits CA IX, CA XII and CA II with an IC50 of 5.6, 7.4 and 430 nM, respectively. CA IX-IN-2 inhibits the proliferation of cancer cell HCT-116, SW480, MDA-MB 231 and MCF-7, with IC50s of 14.63-29.33 μM. CA IX-IN-2 intercalates DNA, arrests cell cycle at G1/S phase, and induces apoptosis in MDA-MB-231. CA IX-IN-2 affects the mitochondrial membrane potential (MMP), increases the intracellular ROS levels, causes mitochondrial damage, and inhibits the cell migration of MDA-MB-231. CA IX-IN-2 exhibits antitumor efficacy in mouse models.
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DTP348
0 ImagesCat. No.: HY-120367CAS No.: 1383370-92-0DTP348 is an inhibitor for carbonic anhydrase IX with a Ki of 8.3 nM in vitro and an IC50 of 19.26 μM in Xenopus oocytes. DTP348 exhibits slight toxicity in zebrafish embryos with LD50 of 3.5 mM. DTP348 can be used in the anti-cancer research.
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Elsulfavirine sodium
0 ImagesCat. No.: HY-109056ACAS No.: 867365-40-0Synonyms: R-1206 sodiumElsulfavirine sodium (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 sodium 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 sodium and Lenvatinib (HY-10981) produces a synergistic anti-tumor effect. Elsulfavirine sodium is converted into the active metabolite VM1500A in vivo, blocks the DNA polymerase activity of reverse transcriptase, and inhibits HIV-1 replication. Elsulfavirine sodium exhibits a Ki of 1960 nM-52400 nM against human carbonic anhydrase isoforms including I, VII, VI, VA, VB, IX, XIII, XIV. Elsulfavirine sodium is used in studies related to HIV-1 infection and liver cancer.
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Carbonic anhydrase inhibitor 33
0 ImagesCat. No.: HY-172899Carbonic anhydrase inhibitor 33 (11D) is a dual inhibitor of CA (Carbonic anhydrase) IX/XII and CDK6, with Ki values of 19.7 nM and 26.1 nM for hCA IX and hCA XII, respectively. Carbonic anhydrase inhibitor 33 (11D) induces G1 arrest and apoptosis. Carbonic anhydrase inhibitor 33 (11D) can be used in the research for NSCLC.
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CA
IX-IN-6
0 ImagesCat. No.: HY-187174CA IX-IN-6 is a selective human carbonic anhydrase IX (hCA IX) inhibitor, with Ki values of 8.9, 50.7, 551, and 64.4 nM against hCA IX, hCA XII, hCA I, and hCA II, respectively. CA IX-IN-6 binds to the active site via a classic sulfamide mode, coordinates with the catalytic Zn2+ ion, forms a hydrogen bond with Thr200, and interacts with key active site residues. CA IX-IN-6 can be used in studies related to tumor-associated carbonic anhydrase inhibition.
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HCAIX-IN-2
0 ImagesCat. No.: HY-146207CAS No.: 2389034-45-9HCAIX-IN-2 (compound 9d) is a selective carbonic anhydrase inhibitor with the Ki values of 24.6 nM and 45.3 nM for hCA IX and hCA XII, respectively.
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CAIX/CDK-2-IN-1
0 ImagesCat. No.: HY-179022CAIX/CDK-2-IN-1 is a dual-acting inhibitor of carbonic anhydrase IX (CA IX) and cyclin-dependent kinase-2 (CDK-2) with IC50 values of 0.29 μM and 0.32 μM. The zein nanoparticls of CAIX/CDK-2-IN-1 can induce cancer cells apoptosis. CAIX/CDK-2-IN-1 can be used for the research of cancer, such as lung cancer.
