CA I Inhibitor

5,6-Dihydro-2H-pyran-2-one (Compound 1) is a prodrug-type carbonic anhydrase inhibitor. 5,6-Dihydro-2H-pyran-2-one can specifically inhibit the tumor-associated subtype hCA IX and the cytoplasmic subtype hCA I with K_i values of 1.35 and 8.03 μM. 5,6-Dihydro-2H-pyran-2-one can be used for the research on hypoxia-related cancer.

Elsulfavirine (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 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 and Lenvatinib (HY-10981) produces a synergistic anti-tumor effect. Elsulfavirine is converted into the active metabolite VM1500A in vivo, blocks the DNA polymerase activity of reverse transcriptase, and inhibits HIV-1 replication. Elsulfavirine exhibits a K_i of 1960 nM-52400 nM against human carbonic anhydrase isoforms including I, VII, VI, VA, VB, IX, XIII, XIV. Elsulfavirine is used in studies related to HIV-1 infection and liver cancer.

4-Chloro-3-sulfamoylbenzoic acid is a weak inhibitor of human carbonic anhydrase isoforms hCA I, hCA II, hCA IV, and hCA IX, and a synthesis intermediate for carbonic anhydrase inhibitors. 4-Chloro-3-sulfamoylbenzoic acid is the major metabolite of tripamide detected in tissues, urine, and feces of rats and rabbits following Tripamide (HY-106570) administration. 4-Chloro-3-sulfamoylbenzoic acid can be used for the study of carbonic anhydrase inhibition and species differences in drug metabolism.

hCAIX-IN-18 (compound 30) is an inhibitor of carbonic anhydrase (CA), with K_is of 3.5 nM, 9.4 nM, 43.0 nM and 8.2 nM for hCAI, hCAII, hCAIX, hCAXII, respectively. hCAIX-IN-18 can be used for cancer research.

COX-2/CA II-2 is an orally active dual selective inhibitor targeting COX-2 and hCA II. COX-2/CA II-2 inhibits COX-2 with an IC₅₀ value of 0.05 μM (SI = 12.02 vs COX-1) and hCA II with a K_i value of 62.6 nM (SI = 704.2 vs hCA I). COX-2/CA II-2 demonstrates significant analgesic and anti-inflammatory effects with rapid onset and sustained duration in animal models, shows improved gastric safety with reduced ulcerogenic liability, and exhibits a gradual intraocular pressure (IOP)-lowering effect without statistical significance relative to the sham-treated eye in rabbit glaucoma models. COX-2/CA II-2 can be used for anti-inflammatory, analgesic and antiglaucoma research.

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.

Methyl acetazolamide (Propazolamide) is a carbonic anhydrase inhibitor with K_i values of 37.5 nM against Enterococcus faecium α-CA, 250.1 nM against Enterococcus faecium γ-CA, 235.4 nM against human CA I, and 37.2 nM against human CA II. Methyl acetazolamide can be used for the research of enterococcus infections.

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.

CAI/II-IN-13 (Compound 5f) is a CAI/II inhibitor, with IC₅₀ values of 309.16 nM for hCA I and 267.27 nM for hCA II. CAI/II-IN-13 exhibits potent and selective antiproliferative activity against A549 lung cancer cells (IC₅₀ = 0.58 μM). CAI/II-IN-13 can be used for the study of lung cancer.

BChE/hCA II-IN-1 (Compound 20) is a dual-functional inhibitor of Butyrylcholinesterase (BChE) and human carbonic anhydrase II (hCA II) with IC₅₀s of 76.50 and 10.69  μM for BChE and hCA II, respectively. BChE/hCA II-IN-1 can be used for neurodegenerative diseases like Alzheimer's and glaucoma research.

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.

CAII-IN-12 (compound 6c) is a potent and selective carbonic anhydrase (CA) II and VII inhibitor (hCA II K_i = 47.8 nM, hCA VII K_i = 3.6 nM) with anti-epilepitic activity. CAII-IN-12 displays selectivity over hCA I (K_i = 370 nM). CAII-IN-12 exhibits potent anticonvulsant activity in both Pentylenetetrazol- and Pilocarpine (HY-B0726A)-induced seizure mouse models. CAII-IN-12 increases expression of KCC2 in the hippocampus, maintains neuronal integrity, and reduces mTOR activity. CAII-IN-12 can be used for epilepsy research.

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.

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.

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.

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.

AChE/hCA I-IN-1 (Compound L3) is the inhibitor for acetylcholinesterase (AChE) and carbonic anhydrase (CA), that inhibits AChE, hCA I and hCA II with IC₅₀ of 302, 265 and 283 nM, respectively.

CAI/II-IN-2 (compound 2b) is a potent dual hCA I/II inhibitor with K_i values of 40.97, 15.15 and 61.88 nM for hCA I, hCA II and hCA Ⅸ. CAI/II-IN-2 possesses anti-hypoxic activity against acute mountain sickness (AMS) and low cellular activity.

Carbonic anhydrase/AChE-IN-1 (compound 16) is a carbonic anhydrase and AChE inhibitor with K_is of 24.42 nM, 19.95 nM, and 5.07 nM for hCA I, hCA II, and AChE, respectively.