| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| Other Sizes |
| Targets |
The primary target of Carboxyamidotriazole is non-voltage-operated calcium channels. By binding to and inhibiting these channels, it blocks both Ca2+ influx into cells and Ca2+ release from intracellular stores. This disruption in calcium signaling leads to the inhibition of PI3 activity and VEGF signaling.
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| ln Vitro |
In LAMA84R and K562R cell lines, carboxyamidotriaz orotate (0.1–10 µM; 24-96 hours) suppresses cell proliferation [1]. Bcr-Abl kinase phosphorylation of specific sites is inhibited by carboxyamidotriaz otate. The application of 5 µM carboxamide triazole orotate inhibits CrkL's tyrosine phosphorylation [1].
In vitro, Carboxyamidotriazole orotate inhibits the phosphorylation of a selected target of Bcr-Abl kinase. Tyrosine phosphorylation of CrkL is reduced by treatment with 5 µM of the compound. This suggests activity against signaling pathways important for cell proliferation and survival. |
| ln Vivo |
CML xenografts were subjected to carboxamide triazole orotate (342, 513 mg/kg; i.p.; two rounds Q1D×5), which exhibited anticancer efficacy [1].
The in vivo activity is related to its antiangiogenic and antiproliferative effects. By inhibiting calcium signaling and VEGF, the compound may inhibit endothelial proliferation, tumor cell growth, invasion, and metastasis. It represents a potential therapeutic strategy for cancer research. |
| Enzyme Assay |
The in vitro mechanism is studied in cell-free systems to confirm target engagement. Assays typically involve measuring the inhibition of calcium ion flux through non-voltage-operated calcium channels in isolated membrane preparations. Alternatively, the binding affinity of the compound to these channels can be assessed.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: LAMA84R and K562R Cell lines Tested Concentrations: 0.1, 1, 5, 10 µM Incubation Duration: 24, 48, 72, 96 hrs (hours) Experimental Results: Shows 50% reduction in chronic myelogenous leukemia (CML) growth) Line with 5 µM CTO at the 96 hour time point. Western Blot Analysis[1] Cell Types: LAMA84R and K562R cell lines Tested Concentrations: 0.1, 1, 5 µM Incubation Duration: 72 and 96 hrs (hours) Experimental Results: Dose-dependent inhibition of total Bcr-Abl levels and phosphorylated Bcr-Abl levels. In vitro cellular assays are performed in various cancer cell lines. The compound's effect on signaling is evaluated by measuring the phosphorylation status of proteins like CrkL, a downstream target of Bcr-Abl kinase, via Western blotting. Cell proliferation and viability assays are used to assess its antiproliferative effects. |
| Animal Protocol |
Animal/Disease Models: Four to five week old male NOD/SCID (severe combined immunodeficient) mouse [1]
Doses: 342, 513 mg/kg Route of Administration: intraperitoneal (ip) injection; Q1D×5 two-round Experimental Results: increased survival rate. In vivo activity is evaluated in animal models of cancer, such as xenograft models. Tumor-bearing mice are treated with Carboxyamidotriazole orotate, and tumor growth is monitored. Endpoints include tumor volume, microvessel density (as a measure of angiogenesis), and analysis of signaling pathway markers in tumor tissue. |
| ADME/Pharmacokinetics |
As an orally bioavailable agent, Carboxyamidotriazole orotate is designed for convenient administration. Its pharmacokinetic properties are suitable for achieving therapeutic concentrations in the systemic circulation. The orotate salt form is used to improve the drug's physicochemical properties and oral bioavailability.
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| Toxicity/Toxicokinetics |
Toxicological data for Carboxyamidotriazole orotate is primarily derived from preclinical studies. As a cytostatic agent, its toxicity profile is likely related to its mechanism of action, affecting rapidly dividing cells. It is not approved for clinical use.
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| References |
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| Additional Infomation |
Carboxyamidotriazole orotate is the orotate form of Carboxyamidotriazole (CAI), a small molecule with high oral bioavailability and potential anti-angiogenic and anti-proliferative activities. Carboxyamidotriazole binds to and inhibits the activity of non-voltage-gated calcium channels, thereby blocking Ca2+ influx into cells and the release of Ca2+ from intracellular storage, ultimately leading to the disruption of calcium channel-mediated signal transduction. CAI can inhibit PI3 activity and vascular endothelial growth factor (VEGF) signaling. This may inhibit endothelial cell proliferation, tumor cell growth, invasion, and metastasis.
Carboxyamidotriazole (CAI) was originally developed by the National Cancer Institute (NCI) as an anti-cancer agent. The orotate salt was investigated to improve its pharmacokinetic properties. While it has shown promise in preclinical studies, its clinical development may have been limited due to its modest efficacy or toxicity profile. |
| Molecular Formula |
C22H16CL3N7O6
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|---|---|
| Molecular Weight |
580.764740943909
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| Exact Mass |
579.022
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| CAS # |
187739-60-2
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| Related CAS # |
Carboxyamidotriazole;99519-84-3
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| PubChem CID |
11599548
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| Appearance |
Light yellow to yellow solid powder
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
38
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| Complexity |
816
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
MNWOBDDXRRBONM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H12Cl3N5O2.C5H4N2O4/c18-10-3-1-9(2-4-10)15(26)13-11(19)5-8(6-12(13)20)7-25-16(21)14(17(22)27)23-24-25;8-3-1-2(4(9)10)6-5(11)7-3/h1-6H,7,21H2,(H2,22,27);1H,(H,9,10)(H2,6,7,8,11)
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| Chemical Name |
5-amino-1-[[3,5-dichloro-4-(4-chlorobenzoyl)phenyl]methyl]triazole-4-carboxamide;2,4-dioxo-1H-pyrimidine-6-carboxylic acid
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~5 mg/mL (~8.61 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7219 mL | 8.6094 mL | 17.2188 mL | |
| 5 mM | 0.3444 mL | 1.7219 mL | 3.4438 mL | |
| 10 mM | 0.1722 mL | 0.8609 mL | 1.7219 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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