CA IX Inhibitor

hCAXII-IN-9 (Compound 3I) is a selective inhibitor of hCAXII with K_i values of 28 nM, 7192.6 nM, 188.6 nM, and >100000 nM for hCAXII, hCAI, hCAII, and hCAIX, respectively. hCAXII-IN-9 can be utilized in antitumor research.

hCAIX/XII-IN-5 (Coumarin 9a) a carbonic anhydrase (CA) inhibitor, and exhibits excellent hCA IX/XII selectivity (K_i=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.

CAXII-IN-3 is an effective carbonic anhydrase (CA XII) inhibitor with a K_i of 53 nM. CAXII-IN-3 exhibits selective inhibition against multiple human CA subtypes with K_is 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.

COX-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 (K_i=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.

α-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 K_i= 7.0 nM. α-Glucosidase-IN-63 is orally effective..

CA/PRAK-IN-1 is a dual inhibitor of carbonic anhydrase (Carbonic Anhydrase) and PRAK, with a K_i 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.

hCAIX/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 K_i 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).

CAIX/XII-IN-17 is a selective human carbonic anhydrase IX/XII (CA IX/XII) inhibitor with K_i 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.

hCAII-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.

hCA-IN-1 (Compound 5u) is an hCA inhibitor with K_i 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.

hCAIX/XII-IN-11 (Compound 6c) is an inhibitor of hCA IX and hCA XII with a K_i value of 0.7 μM for both the isoforms. hCAIX/XII-IN-11 can be used for anticancer research.

Carbonic anhydrase inhibitor 14 (Compound 8b) is a carbonic anhydrase (CA) inhibitor with K_i 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.

CAII-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.

Carbonic anhydrase-IN-37 (compound 9a) is a potent and orally active carbonic anhydrase (CA) inhibitor with K_is 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.

CAIX/XII/NAMPT-IN-1 is a triple inhibitor of carbonic anhydrase IX/XII and nicotinamide phosphoribosyltransferase (NAMPT) with a hCA IX K_i of 78.1 nM, hCA XII K_i 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.

BCS12 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.

hCAIX-IN-24 is a potent and selectively hCA IX inhibitor with an K_I value of 32.1 nM. hCAIX-IN-24 shows anti-proliferative activity.

VEGFR/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 (K_i = 19.4 nM), with weaker activity against hCA I (K_i = 154.2 nM) and hCA IX (K_i = 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).

CAII-IN-14 (Compound 3o) is a human carbonic anhydrase II (hCA II) inhibitor with a K_i value of 1.65 nM. CAII-IN-14 also inhibits hCA I(K_i = 6.15 nM) and hCA IX(K_i = 5.43 nM). CAII-IN-14 exhibits predicted drug-like properties.

hCA IX-IN-1 (Compound 6f) is a human carbonic anhydrase (hCA) inhibitor with K_i 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.