| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 100mg | |||
| Other Sizes |
| Targets |
cAMP receptor / Protein kinase A (PKA). Tocladesine is a cAMP receptor agonist that modulates cAMP-dependent PKA activity.
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|---|---|
| ln Vitro |
In vitro, 8-Chloro-cAMP strongly suppresses the growth of vascular smooth muscle cells (VSMC), lowers the expression of PKA RIIβ subunit, and increases the expression of PKA RIα subunit [1].
In vitro, Tocladesine markedly inhibits vascular smooth muscle cell (VSMC) proliferation. It reduces protein kinase A (PKA) RIα subunit expression and induces PKA RIIβ subunit expression. Tocladesine has anticancer activity. It is a cyclic nucleotide phosphodiesterase (PDE) inhibitor that increases the levels of cAMP and cGMP in cells. |
| ln Vivo |
In a dose-dependent manner, 8-Chloro-cAMP (12 mg/kg) decreased the neointima area and neointima/media ratio following balloon damage in rats. In vivo, 8-Chloro-cAMP can lower VSMC proliferative activity [1].
In vivo, Tocladesine has been investigated for the treatment of colorectal cancer, multiple myeloma, and plasma cell tumors. It possesses potential antitumor activity. Further details on in vivo efficacy are available in the primary research literature. |
| Enzyme Assay |
Non-cell receptor binding assays for Tocladesine are performed using purified PKA regulatory subunits or cAMP-binding proteins. Radioligand binding studies are conducted using [³H]cAMP as a tracer. PKA regulatory subunits are incubated with the radioligand and varying concentrations of Tocladesine (0.001-100 μM). Nonspecific binding is determined with excess unlabeled cAMP. After incubation at 4°C for 60-120 minutes, bound and free ligand are separated by filtration or charcoal adsorption, and radioactivity is counted. IC₅₀ and Ki values are calculated from competition curves.
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| Cell Assay |
Cellular assays for Tocladesine are performed using cancer cell lines (e.g., colorectal cancer, multiple myeloma cells) or vascular smooth muscle cells. Cells are treated with Tocladesine at concentrations ranging from 0.01-100 μM for 24-72 hours. Cell proliferation is assessed using MTT or CellTiter-Glo assays. PKA subunit expression (RIα and RIIβ) is assessed by Western blotting. cAMP levels are measured by ELISA. Cell cycle analysis is performed by flow cytometry. Apoptosis is evaluated by Annexin V staining.
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| Animal Protocol |
In vivo animal studies are conducted in mouse xenograft models using colorectal cancer or multiple myeloma cell lines. Tumor-bearing mice are treated with Tocladesine administered intraperitoneally or intravenously at doses determined from pharmacokinetic studies. Tumor volume is measured by calipers. At study termination, tumors are harvested for histology and biomarker analysis (e.g., PKA subunit expression). The compound's antitumor efficacy is evaluated.
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| ADME/Pharmacokinetics |
Tocladesine has a molecular weight appropriate for a cAMP analog. It is also known as 8-chloro-cAMP, Adenazole, ICN-1256, and NSC-614491. The compound is soluble in water and DMSO. It is typically stored as a powder at -20°C.
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| Toxicity/Toxicokinetics |
Comprehensive toxicology data for Tocladesine are limited. As a cAMP analog, it is expected to have a reasonable safety profile. No significant toxicity has been reported at effective concentrations in preclinical studies. Standard safety pharmacology studies would be required for therapeutic development.
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| References | |
| Additional Infomation |
Tocladixin has been investigated for the treatment of colorectal cancer, multiple myeloma, and plasma cell tumors. Tocladixin is an antimetabolite, a chloride derivative of the intracellular second messenger cyclic adenosine monophosphate (cAMP), and possesses potential antitumor activity. Tocladixin appears to be converted to 8-chloroadenosine by phosphodiesterase, which then phosphorylates it to 8-chloro-ATP, a purine analog that competes with ATP for transcriptional activity. Furthermore, the generation of 8-chloro-ATP depletes the endogenous ATP pool, which is crucial for many biological responses involved in intracellular energy transfer. Therefore, this drug can lead to inhibition of RNA synthesis, impaired cell proliferation, and induction of apoptosis.
Tocladesine (8-chloro-cAMP) is a cyclic adenosine monophosphate (cAMP) receptor agonist and an antimetabolite with potential antitumor activity. It has been investigated for the treatment of colorectal cancer and multiple myeloma. Tocladesine is not approved for clinical use. |
| Molecular Formula |
C10H11CLN5O6P
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|---|---|
| Molecular Weight |
363.65
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| Exact Mass |
363.014
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| Elemental Analysis |
C, 33.03; H, 3.05; Cl, 9.75; N, 19.26; O, 26.40; P, 8.52
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| CAS # |
41941-56-4
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| PubChem CID |
100299
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| Appearance |
White to light yellow solid powder
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| Density |
2.55 g/cm3
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| Boiling Point |
731.7ºC
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| Flash Point |
396.3ºC
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| Index of Refraction |
2.009
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| LogP |
0.417
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| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
23
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| Complexity |
532
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| Defined Atom Stereocenter Count |
4
|
| SMILES |
C1[C@@H]2[C@H]([C@H]([C@@H](O2)N3C4=NC=NC(=C4N=C3Cl)N)O)OP(=O)(O1)O
|
| InChi Key |
CLLFEJLEDNXZNR-UUOKFMHZSA-N
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| InChi Code |
InChI=1S/C10H11ClN5O6P/c11-10-15-4-7(12)13-2-14-8(4)16(10)9-5(17)6-3(21-9)1-20-23(18,19)22-6/h2-3,5-6,9,17H,1H2,(H,18,19)(H2,12,13,14)/t3-,5-,6-,9-/m1/s1
|
| Chemical Name |
(4aR,6R,7R,7aS)-6-(6-amino-8-chloropurin-9-yl)-2-hydroxy-2-oxo-4a,6,7,7a-tetrahydro-4H-furo[3,2-d][1,3,2]dioxaphosphinin-7-ol
|
| Synonyms |
NSC-614491; ICN-1256; Tocladesine; 8-Chloro-cAMP; 41941-56-4; 8-Cl-cAMP; 8-chloro-cyclic AMP; 8 Cl-cAMP
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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 |
| 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) |
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
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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 | 2.7499 mL | 13.7495 mL | 27.4990 mL | |
| 5 mM | 0.5500 mL | 2.7499 mL | 5.4998 mL | |
| 10 mM | 0.2750 mL | 1.3749 mL | 2.7499 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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