| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
hCA I 3.5 nM (IC50) hCA II 9.4 nM (IC50) hCA IX 43 nM (IC50) hCA XII 8.2 nM (IC50)
hCA I (Ki: 3.5 nM), hCA II (Ki: 9.4 nM), hCA IX (Ki: 43.0 nM), hCA XII (Ki: 8.2 nM) |
|---|---|
| ln Vitro |
hCAIX-IN-18 is a potent inhibitor of carbonic anhydrase (CA). It exhibits Ki values of 3.5 nM for hCAI, 9.4 nM for hCAII, 43.0 nM for hCAIX, and 8.2 nM for hCAXII. The compound shows selectivity for hCAI, hCAII, and hCAXII over hCAIX, but the sub-nanomolar Ki for CAI/II indicates broad, potent pan-CA inhibition. CA IX is a tumor-associated isoform upregulated in hypoxic solid tumors. No specific cellular or in vivo data are provided.
|
| ln Vivo |
No specific in vivo data available for hCAIX-IN-18. As a potent CA inhibitor, particularly of the tumor-associated isoform CA IX, it has potential for in vivo efficacy in xenograft models of hypoxic tumors. CA IX inhibition can reduce tumor growth, invasion, and metastasis by altering pH regulation. In vivo studies would involve administration of the compound to tumor-bearing mice to assess tumor volume, pH, and metastasis. However, the broad inhibition of CA I and II may cause on-target toxicities (e.g., metabolic acidosis).
|
| Enzyme Assay |
Recombinant human carbonic anhydrase isozymes (hCA I, hCA II, hCA IX, hCA XII) are expressed in E. coli and purified. The CA activity assay measures the esterase activity of CA using 4-nitrophenyl acetate (NPA) as substrate, or the CO2 hydration activity using a stopped-flow pH indicator method. For the esterase assay: the reaction mixture contains Tris-SO4 buffer (pH 7.4), NPA (0.8 mM), and varying concentrations of hCAIX-IN-18 (0.1-5000 nM). The change in absorbance at 348 nm is monitored. Ki values are determined from dose-response curves (3.5, 9.4, 43.0, 8.2 nM respectively). For CO2 hydration, the reaction is monitored by the change in pH of a buffer.
|
| Cell Assay |
Human cancer cell lines expressing CA IX (e.g., HeLa, SiHa, HT-29, MCF-7) are cultured in DMEM or RPMI-1640 with 10% FBS. Cells are grown under normoxic (21% O2) or hypoxic (1-5% O2) conditions to induce CA IX expression. Cells are treated with hCAIX-IN-18 (0.1-1000 nM) for 24-72 hours. Cell viability is assessed by MTT. CA enzyme activity in cell lysates is measured by CO2 hydration assay. The pH of the culture medium can be monitored. Apoptosis can be assessed by Annexin V/PI staining. Selectivity for CA IX over CA I/II can be evaluated.
|
| Animal Protocol |
No published in vivo animal study for hCAIX-IN-18. A typical protocol for evaluating CA IX inhibitors would involve establishing subcutaneous tumor xenografts in immunodeficient mice (e.g., nude mice) using HT-29 or other CA IX-expressing cancer cell lines. When tumors reach 100-200 mm3, mice are treated with hCAIX-IN-18 formulated in a suitable vehicle (e.g., 10% DMSO, 40% PEG300, 5% Tween 80, 45% saline) and administered intraperitoneally (i.p.) at doses of 10-100 mg/kg daily for 2-4 weeks. Endpoints: tumor volume, pH measurement using pH-sensitive probes, intratumoral CA activity, and metastasis assessment.
|
| ADME/Pharmacokinetics |
No specific PK data for hCAIX-IN-18. The compound has MW 394.88, which is moderate. LogP can be estimated from the structure (likely ~2-3). The compound contains a sulfonamide group (typical of CA inhibitors), which may improve solubility and oral absorption. No PK parameters (half-life, Cmax, AUC, clearance) are publicly available. Solubility: DMSO (20-50 mg/mL). For in vivo formulation, 10% DMSO + 40% PEG300 + 5% Tween80 + 45% saline can be used.
|
| Toxicity/Toxicokinetics |
No specific toxicity data for hCAIX-IN-18. As a potent pan-CA inhibitor (especially CA I and II), the primary expected on-target toxicity is metabolic acidosis due to inhibition of renal CA. Other side effects include paresthesia (tingling), altered taste (dysgeusia), diuresis, and fatigue. The compound may also cause hepatotoxicity due to the nitro group (potential for nitroreduction and reactive metabolite formation). For research use, handle with standard precautions; avoid inhalation and skin contact.
|
| References | |
| Additional Infomation |
hCAIX-IN-18 (compound 30, CAS: 2925261-76-1) is a potent carbonic anhydrase inhibitor developed as a research tool for studying the role of CA IX in cancer biology. CA IX is a tumor-associated isoform upregulated in hypoxic solid tumors, where it contributes to extracellular acidification and promotes invasion and metastasis. This compound is a sulfonamide derivative (C17H19ClN4O3S, MW 394.88). It is not approved for clinical use. For research use only. References: Singh S, et al. (2020).
|
| Molecular Formula |
C17H19CLN4O3S
|
|---|---|
| Molecular Weight |
394.88
|
| Exact Mass |
394.087
|
| CAS # |
2925261-76-1
|
| PubChem CID |
171356273
|
| Appearance |
White to off-white solid powder
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
26
|
| Complexity |
586
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1CN(CCN1C2=CC=C(C=C2)S(=O)(=O)N)/C(=N/O)/C3=CC=C(C=C3)Cl
|
| InChi Key |
WOCYSDBHUJLEPT-LVZFUZTISA-N
|
| InChi Code |
InChI=1S/C17H19ClN4O3S/c18-14-3-1-13(2-4-14)17(20-23)22-11-9-21(10-12-22)15-5-7-16(8-6-15)26(19,24)25/h1-8,23H,9-12H2,(H2,19,24,25)/b20-17+
|
| Chemical Name |
4-[4-[(E)-C-(4-chlorophenyl)-N-hydroxycarbonimidoyl]piperazin-1-yl]benzenesulfonamide
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| 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 | 2.5324 mL | 12.6621 mL | 25.3241 mL | |
| 5 mM | 0.5065 mL | 2.5324 mL | 5.0648 mL | |
| 10 mM | 0.2532 mL | 1.2662 mL | 2.5324 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
