xii

Bismuth subgallate (Dermatol Puder) is an astringent and antiseptic and is applied to skin diseases such as eczema.

CAIX Inhibitor S4 (S4) is an effective inhibitor of carbonic anhydrase IX/XII with a Ki of 7 nM and 2 nM, respectively. The Kis for CA II and CA I are 546 and 5600 nM.

Calpain Inhibitor XII (Z-L-Nva-CONH-CH2-2-Py) is a selective and potent inhibitor of calpain I, inhibits calpain II and cathepsin B. Calpain Inhibitor XII shows antiviral activity against coronavirus in cell culture.

hCAII/XII-IN-1 (compound 4l) is a potent inhibitor of hCAXII and hCAII, with Ki values of 8.4 nM and 9.4 nM, respectively. It plays a significant role in cancer research.

hCAIX/XII-IN-14 (Compound 1i) is an inhibitor of hCAIX and hCAXII, with Ki values of 9.4 nM for hCAII, 5.6 nM for hCAIX, and 6.3 nM for hCAXII.

hCAIX/XII-IN-15 (Compound 17β) is an inhibitor of hCA IX and hCA XII, exhibiting Ki values of 0.42 and 4.37 μM, respectively. It demonstrates a pro-apoptotic effect in multiple myeloma cells.

hCAIX/XII-IN-9 (compound 8) is a potent inhibitor of carbonic anhydrase (CA), with Ki values of 1658 nM for hCA I, 184.8 nM for hCA II, 8.9 nM for hCA IX, and 64.8 nM for hCA XII.

hCAIX/XII-IN-10 (compound DK-8) is an inhibitor of Carbonic Anhydrase, showing potent inhibitory activity against the tumor-associated membrane-bound isoforms hCA IX and XII, with Ki values of 32.5 nM and 29.2 nM, respectively.

PDGFRA/CAIX/XII-IN-1 is a multi-target inhibitor targeting PDGFRA, CA IX and CA XII, with an IC50 of 20 nM against PDGFRA and Ki values of 93.3 nM and 80.0 nM against CA IX and CA XII respectively. It targets and binds to the ATP-binding pocket of PDGFRA, thereby blocking the activation of downstream signaling pathways such as STAT3, AKT and ERK1/2. It induces G0/G1 phase cell cycle arrest and initiates endogenous apoptotic procedures, manifested as cleavage and activation of PARP-1, caspase-9 and caspase-3, upregulation of caspase 3/7 activity and inhibition of Mcl-1 protein expression. It exerts significant anti-proliferative effects in eosinophilic leukemia cells and can serve as a candidate tool compound for mechanism and efficacy research of leukemia.

hCAIX/XII-IN-12 (Compound 6) is a potent and highly selective dual inhibitor of hCA IX and hCA XII, exhibiting Ki values of 8.2 nM and 5.6 nM, respectively. This compound demonstrates significant antiproliferative activity against colon cancer cells, maintaining its effectiveness even under hypoxic conditions, and is applicable in colon cancer research.

CAIX/XII/NAMPT-IN-1 is a triple inhibitor targeting carbonic anhydrase IX/XII (CAIX/XII) and nicotinamide phosphoribosyltransferase (NAMPT), with a Ki of 78.1 nM for hCA IX, a Ki of 64.4 nM for hCA XII, and an IC50 of 168 nM for hNAMPT. It induces apoptosis, promotes the accumulation of reactive oxygen species (ROS), inhibits the ERK/AKT signaling pathway, blocks DNA synthesis, and disrupts mitochondrial function. CAIX/XII/NAMPT-IN-1 exhibits antiproliferative effects on various cancer cells under both normoxic and hypoxic conditions. This compound is useful for cancer research, including studies on renal cancer, glioblastoma, and colorectal cancer.

hCAIX/XII-IN-5 (Coumarin 9a) is an inhibitor of carbonic anhydrase (CA) with excellent selectivity for hCA IX/XII, displaying Kis of 93.3 nM and 85.7 nM over hCA I and hCA II, respectively. It exhibits anti-proliferative activities in cancer cells, delaying the cell cycle and inducing apoptosis [1].

hCAIX/XII-IN-2 (compound 6a) is a potent and selective inhibitor of hCAIX and hCAXII, with Ki values of >10000 nM for hCAI and hCAII, and 30.0 nM and 3.6 nM for hCAIX and hCAXII respectively [1].

hCAIX/XII-IN-4 (compound 6c) is a highly potent inhibitor of CAIX/XII, exhibiting Ki values of 4.5 nM for CAXII, 23.6 nM for CAIX, and >10000 nM for both CAI and CAⅡ, respectively [1].

hCAIX/XII-IN-1, a potent inhibitor of both CAIX and CAXII, exhibits KI values of 0.48 μM for CAIX and 0.83 μM for CAXII, respectively. This compound demonstrates antiproliferative activity in vitro and induces apoptosis in MCF-7 cells [1].

hCAIX/XII-IN-3 (compound 6q) is a potent, selective inhibitor of hCAIX and hCAXII, with K i values of >10000 nM for hCAI and hCAII, and 66.2 nM and 4.4 nM for hCAIX and hCAXII, respectively.

hA2A/hCA XII modulator 1 is a potent antagonist of the hA2A adenosine receptor (hA2AAR), a triazolopyrazine that acts on hA2AAR (Ki: 6.4 nM), hA1AR (Ki: 4.819 μM), and hA3AR (Ki>30 μM). hA2A/hCA XII modulator 1 Also a potent inhibitor of human carbonic anhydrase XII (hCA XII), capable of acting on hCA XII (Ki: 6.2 nM), hCA II (Ki: 46 nM), hCA IX (Ki: 466 nM) and hCA I (Ki: 8.351 μM). hA2A/hCA XII modulator 1 exhibits potential for cancer research.

hCA XII/II/IX-IN-1 is a potent inhibitor of human carbonic anhydrase (hCA), acting on hCA I (IC50: 2.6 μM), hCA II (IC50: 0.004 μM), hCA IX (IC50: 0.005 μM), and hCA XII (IC50: 0.001 μM). hCA XII/II/IX-IN-1 exhibited anticancer effects.

hCAIX/XII-IN-6, an orally active carbonic anhydrase (CA) inhibitor, targets human CA isoforms hCA I, II, IV, IX, and XII with inhibition constants (K i) of 6697 nM, 2950 nM, 4093 nM, 4.1 nM, and 7.7 nM, respectively. This compound is utilized in rheumatoid arthritis (RA) research.

Compound 4d, known as hCA XII-IN-6, is a potent inhibitor of human carbonic anhydrase XII (hCA XII) with a Ki value of 84.2 nM and exhibits anti-proliferative effects, making it useful in cancer research [1].

JH-XII-03-02 is a potent, selective leucine-rich repeat kinase 2 (LRRK2) proteolysis targeting chimera (PROTAC) degrader, utilized in Parkinson's Disease (PD) research [1].

Compound 3e (hCAIX/XII-IN-7) is a potent inhibitor of human carbonic anhydrase (hCA) isozymes IX and XII, displaying inhibitory constants (Kis) of 503.7 nM for hCA IX and 59 nM for hCA XII, while also showing activity against hCA I and II with Kis of 3.2 nM and 9.2 nM, respectively. It holds potential for research into hypoxic tumors [1].

hCAIX/XII-IN-8 (compound 3g) is a potent inhibitor of the human carbonic anhydrases (CAs) IX and XII, with inhibition constants (K i) of 8.5 nM for CA IX and 6.7 nM for CA XII. It demonstrates significant inhibitory efficacy particularly against tumor-associated, membrane-bound isoforms hCA IX and XII, while exhibiting high selectivity over the cytosolic isoforms hCA I and II [1].

Jingzhaotoxin-XII (JzTx-XII) functions as a potent inhibitor of the Kv4.1 channel, exhibiting an inhibitory concentration (IC50) of 0.363 μM. It modulates the channel's gating behavior [1].