| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg | |||
| Other Sizes |
| Targets |
CD4 (cluster of differentiation 4); also Sec61α.
|
|---|---|
| ln Vitro |
Without changing the expression of any other cellular receptor tested so far, clotiazadisulfonamide (CADA) dramatically lowers the quantity of cell surface CD4, the main HIV receptor [1]. Cyclotriazadisulfonamide (CADA) has an EC50 of 0.4 μg/mL against CD4 in MO-DC cells. MO-DC treated with 10 μg/mL CADA showed an 83% downregulation of cell surface CD4, which is comparable to what is seen when CD4+ T cells are treated with CADA [1]. With EC50 values of 0.7 and 1.2 g/ml, respectively, CADA shields MT-4 cells against HIV-1 and SIV infection [1]. A specific inhibitor of the Sec61 translocon is cyclotriazadisulfonamide. Measuring the proteome of T cells revealed that only five cyclic triazabisulfonamide substrates (huCD4, SORT, CD137, DNAJC3, PTK7, and ERLEC1) had IC50 values between 0.2 and 2 µM [3].
CADA inhibits HIV at submicromolar levels by specifically down-modulating cell-surface and intracellular CD4 expression. CADA significantly reduces the number of CD4 molecules on the cell surface without altering the expression of any other cellular receptor detected to date. The EC50 of CADA is 0.4 µM in MO-DC cells. Treatment of MO-DC with CADA at 10 µg/mL results in downregulation of 83% of cell surface CD4. CADA protects MT-4 cells from infection with HIV-1 and SIV with EC50 values of 0.7 and 1.2 µg/mL, respectively. The compound inhibits the co-translational translocation of CD4 into the endoplasmic reticulum lumen. |
| ln Vivo |
In vivo efficacy of CADA has been studied in animal models of HIV infection and other diseases where CD4 modulation is relevant. As an HIV entry inhibitor, CADA has been investigated for its potential as a topical microbicide to prevent HIV transmission. The compound has also been studied in models of autoimmune diseases and transplantation where modulation of CD4 expression may have therapeutic benefits. Specific dosing regimens and detailed efficacy data are available in the primary literature but not extensively detailed in public search results.
|
| Enzyme Assay |
CD4 down-modulation is assessed in vitro using cell-based assays. Cells (e.g., MO-DC, MT-4, CD4+ T cells) are treated with CADA at various concentrations (typically 0.01-100 µg/mL). Cell surface and intracellular CD4 levels are measured by flow cytometry using anti-CD4 antibodies. The EC50 for CD4 down-modulation is calculated from dose-response curves. HIV inhibition is assessed using HIV infection assays in susceptible cell lines (e.g., MT-4 cells). The EC50 for protection against HIV-1 and SIV infection is determined.
|
| Cell Assay |
Western blot analysis[1]
Cell Types: MO-DC. Tested Concentrations: 0.4 μg/ml. Incubation Duration: 24 hrs (hours). Experimental Results: CD4 expression was diminished by 50%. Cellular activity is evaluated in CD4+ T cells, MO-DC cells, or MT-4 cells. Cells are treated with CADA at various concentrations (typically 0.01-100 µg/mL) for 24-72 hours. Cell surface CD4 expression is measured by flow cytometry using anti-CD4 antibodies. Intracellular CD4 levels may also be measured. HIV infection is assessed by measuring viral replication (e.g., p24 antigen production) or by using reporter viruses. Cell viability is assessed by MTT or trypan blue exclusion to ensure that CD4 down-modulation is not due to cytotoxicity. |
| Animal Protocol |
In vivo studies for CADA are conducted in animal models of HIV infection (e.g., humanized mouse models) or other diseases. The compound is administered via various routes (topical, oral, intravenous). CD4 expression is measured in blood and tissues by flow cytometry. Viral load is measured in HIV infection models. Pharmacodynamic markers include CD4 down-modulation and reduction of HIV infection. Specific protocols are detailed in the primary literature.
|
| ADME/Pharmacokinetics |
CADA (Cyclotriazadisulfonamide) has a molecular formula of C31H39N3O4S2 and a molecular weight of 581.79 g/mol. CAS Number: 182316-44-5. Appearance: Solid powder. LogP: 4.7. Purity is typically >98%. The compound is soluble in DMSO. Storage: Store at -20°C. It is a macrocyclic molecule with a triazacyclododecane core.
|
| Toxicity/Toxicokinetics |
Safety data for CADA indicate it is a research compound for laboratory use only. As a CD4-targeted HIV entry inhibitor, it may have effects on the immune system by modulating CD4 expression. Specific toxicological profiles including acute toxicity, organ toxicity, genotoxicity, and reproductive toxicity are not extensively published. Standard laboratory safety practices should be followed during handling, including the use of personal protective equipment and adequate ventilation. The compound is for research use only and not for human therapeutic applications without appropriate regulatory approval.
|
| References |
|
| Additional Infomation |
CADA (Cyclotriazadisulfonamide) is a research tool compound for studying CD4 biology, HIV entry, and Sec61 function. It is not approved for clinical use. The compound has been investigated for its potential as a topical microbicide for the prevention of HIV transmission. CADA's mechanism of action involves the specific down-modulation of CD4 expression by inhibiting the co-translational translocation of CD4 into the ER lumen at Sec61α. This unique mechanism distinguishes CADA from other HIV entry inhibitors that target the virus or its receptors directly. CADA is a valuable tool for understanding the regulation of CD4 expression and for developing new strategies for HIV prevention and treatment.
|
| Molecular Formula |
C31H39N3O4S2
|
|---|---|
| Molecular Weight |
581.79
|
| Exact Mass |
581.238
|
| CAS # |
182316-44-5
|
| PubChem CID |
466371
|
| Appearance |
White to off-white solid powder
|
| LogP |
6.812
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
40
|
| Complexity |
928
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC1=CC=C(C=C1)S(=O)(=O)N2CCCN(CCCN(CC(=C)C2)S(=O)(=O)C3=CC=C(C=C3)C)CC4=CC=CC=C4
|
| InChi Key |
SRJIECKMPIRMJJ-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C31H39N3O4S2/c1-26-11-15-30(16-12-26)39(35,36)33-21-7-19-32(25-29-9-5-4-6-10-29)20-8-22-34(24-28(3)23-33)40(37,38)31-17-13-27(2)14-18-31/h4-6,9-18H,3,7-8,19-25H2,1-2H3
|
| Chemical Name |
9-benzyl-3-methylidene-1,5-bis-(4-methylphenyl)sulfonyl-1,5,9-triazacyclododecane
|
| Synonyms |
CADA; Cyclotriazadisulfonamide
|
| 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) |
DMSO : ~33.33 mg/mL (~57.29 mM)
|
|---|---|
| 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 | 1.7188 mL | 8.5942 mL | 17.1883 mL | |
| 5 mM | 0.3438 mL | 1.7188 mL | 3.4377 mL | |
| 10 mM | 0.1719 mL | 0.8594 mL | 1.7188 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
