xii

(Rac)-Calpain Inhibitor XII is a reversible and selective inhibitor targeting calpain I (μ-calpain) with a Ki value of 19 nM. It exhibits lower affinities for calpain II (m-calpain, Ki=120 nM) and cathepsin B (Ki=750 nM). This compound is potentially useful for investigating calpains' involvement in various processes such as neutrophil chemotaxis, neuronal signaling, and cardiac responses to injury [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].

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 and selective leucine-rich repeat kinase 2 (LRRK2) proteolysis targeting chimera (PROTAC) degrader, utilized in Parkinson's Disease (PD) research [1].

hCA XII/II/IX-IN-1 is a potent inhibitor of human carbonic anhydrase (hCA) and is able to act 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-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. hCAIX/XII-IN-3 shows K i values of >10000, >10000, 66.2, 4.4 nM for hCAI, hCAII, hCAIX and hCAXII, respectively .

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

hCAIX/XII-IN-5 (Coumarin 9a) is an inhibitor of carbonic anhydrase (CA) that shows excellent hCA IX/XII selectivity with Kis of 93.3 and 85.7 nM over hCA I and hCA II, respectively. hCAIX/XII-IN-5 has anti-proliferative activities to cancer cells that can delay cell cycle and induce apoptosis [1].

RA-XII is a useful organic compound for research related to life sciences. The catalog number is T125868 and the CAS number is 143343-98-0.

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.

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

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.

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 a high selectivity over the cytosolic isoforms hCA I and II [1].

Eupteleasaponin XII is a useful organic compound for research related to life sciences. The catalog number is T125110 and the CAS number is 290809-58-4.

GSK-3 Inhibitor XIII, an ATP-competitive GSK-3 inhibitor (Ki: 24 nM), can be used to study diabetes and obesity.

MDK-4683, also known as CA IX/XII Inhibitor, is a hCA IX and hCA XII inhibitor.

Z-Ile-Leu-aldehyde is an effective and competitive peptide aldehyde inhibitor of γ-secretase and notch.

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

XIIa-IN-1-IN-3 (Compound 22) is a Factor XIIa inhibitor with an apparent inhibition constant (K i app) of 97.8 nM, utilized in the study of thrombosis [1].

Gypenoside XIII is belonging to the gypenosides. Gypenosides, extracted from Gynostemma pentaphyllum, protect against cardiovascular diseases, especially atherosclerosis.

XIIa-IN-1-IN-2 (Compound 21) serves as a potent Factor XIIa inhibitor with an apparent inhibition constant (K i app) of 62.2 nM, utilized primarily in thrombosis research [1].

Bupleuroside XIII, a hepatoprotective natural saponin [1], exhibits properties that safeguard liver function.

hCAII-IN-9 is a potent carbonic anhydrase inhibitor that inhibits hCA II, hCA IX, and hCA XII with IC50s of 1.18 μM and 0.17 μM , and 2.99 μM , respectively. hCAII-IN-9 is not blood-brain barrier permeable.

Compound PDK0269, as 5-HT3 receptor agonists(3–100 μM, pEC50 5.05±0.06), acutely increased XII (hypoglossal) burst frequency and regularity, and decreased bursts/episode . Phenylbiguanide produced a dose-related (10-500 microM) increase in the release of dopamine (280-2000%). When nomifensine (5 microM) was included in the Ringer solution, the effect of Compound PDK0269 on the release of dopamine was ameliorated or inhibited.

Carbonic anhydrase inhibitor 6 is a potent human carbonic anhydrase (hCA) inhibitor that inhibits hCA IX, hCA II, hCA XII, and hCA I. It is used in the study of diseases caused by abnormalities in carbonic anhydrase.

hCAXII-IN-3 (Compound 6o) is a selective inhibitor of human carbonic anhydrase XII (hCAXII) (Ki: 10.0 nM).

CAXII-IN-1 (Compound 17) has antitumor activity that is a selective inhibitor of CA XII. The Ki values of CAXII-IN-1 for hCA XII and hCA IX is 3.8 nM and 56.0 nM, respectively [1].

hCAXII-IN-4 is a selective and potent CA XII inhibitor with a Ki value of 6.4 nM for human CA XII.

hCAXII-IN-2 (compound 5i) is a potent inhibitor of human carbonic anhydrase XII (hCA XII) (Ki: 84.2 nM) and hCA IX (Ki: 268.5 nM), with low activity against hCA I and hCA II.

hCAXII-IN-1 demonstrates selective inhibition of tumor-related subtypes HCA IX and XII, making it potential leading molecules in the development of novel cancer therapeutic drugs with new mechanisms of action.

hCAXII-IN-7 (compound 6e) functions as an inhibitor of human carbonic anhydrase XII (hCA XII) and possesses blood-brain barrier (BBB) permeability. Moreover, it promotes apoptosis in 786-0, SF-539, and HS 578 T cell lines [1].

μ-Conotoxin SxIIIC, an irreversible NaV channel inhibitor, is derived from Conus striolatus and is useful in researching neurological disorders, including chronic pain [1].

hCAXII-IN-5 (compound 6o) is a highly effective and specific inhibitor of hCAXII. The compound exhibits impressive binding affinities, with Ki values of >10000, >10000, 286.1, and 1.0 nM for hCAI, hCAII, hCAIX, and hCAXII, respectively [1].

GSK3i XIII (GSK3 inhibitor XIII) is a GSK-3 ATP-binding site inhibitor.

Ellagic acid (Gallogen) is a fused four ring compound isolated from the kino of Eucalyptus maculata Hook and E. Hemipholia F. Muell. Activates Factor XII of the blood clotting system which also causes kinin release; used in research and as a dye.

Compound 1e, also known as ALP/Carbonic anhydrase-IN-1, is a dual inhibitor targeting both carbonic anhydrase (CA) isozymes II, IX, and XII, as well as alkaline phosphatase (ALP). It exhibits inhibitory IC50 values of 0.44 µM for CA-II, 1.61 µM for CA-IX, 0.51 µM for CA-XII, and 0.107 µM for ALP [1].

Enpp Carbonic anhydrase-IN-2 is a potent dual inhibitor of Enpp and carbonic anhydrase, inhibiting NPP1, NPP2, NPP3, CA-IX, CA-XII, with IC50 values of 1.13, 1.07, 0.74, 0.33, 0.68, respectively.Enpp Carbonic anhydrase-IN-2 induced apoptosis.Enpp Carbonic anhydrase-IN-2 has antiproliferative activity against cancer cells and low cytotoxicity against normal cells.

hCA/Wnt/β-catenin-IN-1 (Compd 15) serves as an inhibitor with selective affinity for hCA isoforms II, IX, and XII, exhibiting K i values of 33.6, 24.1, and 6.8 nM, respectively. Additionally, this compound attenuates P-gp activity and impedes the Wnt/β-catenin signaling pathway. Furthermore, it compromises the viability of cancer cells, specifically targeting the NCI/ADR-RES DOX-resistant cell line [1].

Chlorthalidone impurity G is a potential impurity found in commercial preparations of chlorthalidone that has moderate antihypertensive effects. Chlorthalidone is a thiazide-like diuretic that inhibits the Na+/Cl- cotransporter in the distal convoluted tubule of the kidney, which prevents reabsorption of sodium and chloride leading to a reduction in plasma volume and cardiac output. It also inhibits carbonic anhydrase (CA), including the isoforms CAVB, VII, IX, XII, and XIII (Kis = 2.8-23 nM) and, to a lesser extent, CAI, CAII, IV, VA, and VI (Kis = 138-1,347 nM), which may mediate its sustained vasodilatory activity. Dietary administration of chlorthalidone (8 mg per animal per day) reduces arterial hypertension and prevents or reduces ventricular hypertrophy induced by deoxycorticosterone acetate (DOCA) in salt-hypertensive rats. Formulations containing chlorthalidone have been used alone or in combination with other antihypertensive agents to lower arterial blood pressure and as adjuvants to address edema caused by cardiac or renal disorders.

Anionic interaction of Beta-amyloid (1-11) with Factor XII is suspected to cause massive activation of the C4 (complement 4) system in the cerebrospinal fluid of Alzheimer’s disease patients.

Garadacimab (CSL312) is a potent whole-human IgG4 monoclonal antibody targeting activation factor XII (FXIIa). Garadacimab can be used to study hereditary angioedema.

D-Pro-Phe-Arg-Chloromethylketone, an inhibitor of coagulation factor XII and plasma kallikrein, is significant in the regulation of thrombosis and inflammation [1].

COX-2-IN-31 (compound 7b) is an orally active dual inhibitor targeting COX-2 (IC50=60 nM) and 5-LOX (IC50=1.9 μM). Additionally, it inhibits the activity of transmembrane hCA IX (Ki=48.9 nM) and hCA XII (Ki=5.8 nM). This compound demonstrates anti-inflammatory and analgesic activity [1].

hCAII-IN-2 is a cytoplasmic human carbonic anhydrase (hCA) inhibitor that acts on hCA I (Ki: 261.4 nM), hCA II (Ki: 3.8 nM), hCA IX (Ki: 19.6 nM) and hCA XII (Ki: 45.2 nM).

Compound 6f, also known as hCA IX-IN-1, is a human carbonic anhydrase (hCA) inhibitor that exhibits varying inhibitory effectiveness across different hCA isoforms, with K i values of 331.4 nM for hCA I, 28.4 nM for hCA II, 9.4 nM for hCA IX, and 17.8 nM for hCA XII. It is notable for its anticancer activity [1].

HCAIX-IN-2 (compound 9d) is a selective inhibitor of carbonic anhydrase and acts on hCA IX (Ki: 24.6 nM) and hCA XII (Ki: 45.3 nM).

hCAII-IN-3 (Compound 16) is an inhibitor of human carbonic anhydrase (hCA). It exhibits high affinity for hCA I, hCA II, hCA IX, and hCA XII, with Ki values of 403.8 nM, 5.1 nM, 10.2 nM, and 5.2 nM, respectively. Notably, hCA IX-IN-2 demonstrates anticancer activity [1].

(E)-Dehydrodiconiferyl alcohol is a potent dual inhibitor of hCA IX and hCA XII, effectively impeding the catalytic activity of both carbonic anhydrase isoforms. Additionally, (E)-Dehydrodiconiferyl alcohol exerts inhibitory effects on the nuclear translocation of NF-κB in the connective tissue of the healing area.