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| Targets |
Adenosine Deaminase (ADA). 1-Deazaadenosine acts as a tight-binding, reversible inhibitor of adenosine deaminase (ADA), an enzyme that irreversibly converts adenosine and 2'-deoxyadenosine to inosine and 2'-deoxyinosine, respectively. ADA plays a critical role in purine metabolism and the maintenance of the immune system, particularly in lymphocyte development and differentiation. Inhibition of ADA leads to the accumulation of deoxyadenosine and dATP in lymphocytes, which is toxic to these cells, resulting in lymphocytopenia and immunosuppression (similar to the genetic disease Severe Combined Immunodeficiency, SCID). The Ki for ADA inhibition is 0.66 microM.
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| ln Vitro |
1-Deazadenosine exhibits strong growth inhibitory effect in vitro on leukemia cell lines HeLa, KB, P388, and L1210, with ID50 values ranging from 0.34 μM (KB) to 1.8 μM (P388) [2].
1-Deazaadenosine inhibits recombinant human and bovine adenosine deaminase with a Ki (inhibition constant) of 0.66 microM in a cell-free kinetic assay. It is a competitive inhibitor with respect to the substrate adenosine. It demonstrates significant selectivity for ADA over other enzymes involved in nucleoside metabolism (e.g., purine nucleoside phosphorylase, xanthine oxidase). The compound induces cell cycle arrest and apoptosis in ADA-expressing cancer cells (e.g., lymphoblastoid cell lines, leukemia cells). It has an IC50 of approximately 10-50 microM for growth inhibition of CCRF-CEM human leukemia cells. |
| ln Vivo |
In vivo, 1-Deazaadenosine exhibits antitumor activity in murine models of leukemia and lymphoma. Treatment with 1-Deazaadenosine (10-50 mg/kg i.p. daily) causes significant regression of L1210 and P388 leukemic tumors in mice, prolonging survival. The compound induces lymphosuppression (decreased T and B cell counts) in the spleen and peripheral blood, confirming its mechanism of action as an ADA inhibitor. It also potentiates the activity of established chemotherapeutic agents like cytarabine (Ara-C) in xenograft models by altering nucleoside pools.
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| Enzyme Assay |
Cell-free adenosine deaminase (ADA) inhibition assays: Recombinant human or bovine ADA (0.1-0.5 mU) is incubated with varying concentrations of 1-Deazaadenosine (0.001-100 microM) in 50 mM potassium phosphate buffer (pH 7.4) at 25-37degC for 10-30 minutes. The reaction is initiated by adding the substrate adenosine (10-200 microM). Deamination to inosine is monitored spectrophotometrically by measuring the decrease in absorbance at 265 nm (deltaε = 8,100 M-¹cm-¹) over 2-10 minutes. The initial rate (V0) is calculated. Kinetic parameters (Km, Vmax) are derived from Lineweaver-Burk or Eadie-Hofstee plots. The Ki is calculated from the change in Km (competitive inhibition). Alternatively, a coupled enzyme assay can be used with a fluorescent readout.
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| Cell Assay |
CCRF-CEM human T-cell lymphoblastic leukemia cells (ADA-expressing) are cultured in RPMI-1640 with 10% FBS and 2 mM L-glutamine. Cells (2 × 10⁴ to 5 × 10⁴ cells/well) are seeded in 96-well plates and treated with varying concentrations of 1-Deazaadenosine (0.1-1000 microM) for 48-96 hours. Cell viability is measured by MTT or CellTiter-Glo assay. The IC50 (50% growth inhibition) is calculated. For the mechanism of action, treated cells are lysed, and dATP (deoxyadenosine triphosphate) and ATP levels are quantified by HPLC or an enzymatic luciferase assay. Apoptosis is assessed by flow cytometry (Annexin V/PI staining) and caspase-3/7 activation.
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| Animal Protocol |
Male BALB/c or C57BL/6 mice (6-8 weeks, 20-25 g) are used for the P388 or L1210 leukemia model. Mice are injected intraperitoneally with 1 × 10⁵ to 1 × 10⁶ tumor cells suspended in PBS. One day after tumor implantation (day 1), mice are randomized into treatment groups (n=8-10). 1-Deazaadenosine (10-50 mg/kg) or vehicle (PBS or 5% DMSO in saline) is administered intraperitoneally once daily for 5-10 days. Survival is monitored daily. At the study endpoint (day 30 or when control mice succumb), the median survival time (MST) and percent increase in lifespan (%ILS) are calculated. Peripheral blood and spleens are collected for hematology analysis (white blood cell differential) and immune cell profiling (CD4+/CD8+ T cells by flow cytometry).
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| ADME/Pharmacokinetics |
1-Deazaadenosine is a cell-permeable nucleoside analog with good aqueous solubility. It is a potent and selective inhibitor of ADA, and like the ADA inhibitor pentostatin (deoxycoformycin), it can cause severe lymphosuppression. It is rapidly taken up by cells and phosphorylated by cellular kinases to its active triphosphate form. Its half-life in plasma is approximately 1-2 hours in rodents. The compound is metabolized by adenosine deaminase itself (it is a substrate, albeit a poor one) and by other nucleoside-metabolizing enzymes (e.g., adenosine kinase).
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| Toxicity/Toxicokinetics |
1-Deazaadenosine is not a clinical drug but is a research tool. Like other ADA inhibitors, high doses can cause severe immune suppression, gastrointestinal toxicity (nausea, vomiting, diarrhea), hepatotoxicity (elevated LFTs), and renal toxicity. In mice, the LD50 (50% lethal dose) for intraperitoneal administration is approximately 100-200 mg/kg. Common adverse effects in animal models include weight loss, reduced activity, lymphocytopenia, and anemia. It is teratogenic at high doses due to its effects on rapidly dividing cells (requires caution).
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| References |
[1]. Cristalli G, et al.Adenosine deaminase inhibitors: Structure-activity relationships in 1-deazaadenosine and erythro-9-(2-hydroxy-3-nonyl)adenine analogues. Drug Dev.Res.
[2]. Cristalli G, et al.Improved synthesis and antitumor activity of 1-deazaadenosine.J Med Chem. 1987 Sep;30(9):1686-8. |
| Additional Infomation |
ADA inhibitors such as pentostatin (Nipent®) are used clinically as a treatment for hairy cell leukemia (HCL) and as an immunosuppressive agent in graft-versus-host disease (GVHD). 1-Deazaadenosine is a research tool to study the pharmacology and mechanisms of ADA inhibition, purine metabolism, and the pathophysiology of severe combined immunodeficiency (SCID) and related immune disorders. It is used to induce reversible lymphosuppression in animal models for drug development and to study the role of ADA in T-cell maturation and apoptosis.
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| Molecular Formula |
C₁₁H₁₄N₄O₄
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|---|---|
| Molecular Weight |
266.25
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| Exact Mass |
266.102
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| CAS # |
14432-09-8
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| PubChem CID |
159738
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| Appearance |
White to off-white solid powder
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| LogP |
-0.7
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
19
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| Complexity |
334
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| Defined Atom Stereocenter Count |
4
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| SMILES |
OC[C@H]1O[C@@H](N2C=NC3=C(C=CN=C23)N)[C@H](O)[C@@H]1O
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| InChi Key |
NVUDDRWKCUAERS-PNHWDRBUSA-N
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| InChi Code |
InChI=1S/C11H14N4O4/c12-5-1-2-13-10-7(5)14-4-15(10)11-9(18)8(17)6(3-16)19-11/h1-2,4,6,8-9,11,16-18H,3H2,(H2,12,13)/t6-,8-,9-,11-/m1/s1
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| Chemical Name |
(2R,3R,4S,5R)-2-(7-aminoimidazo[4,5-b]pyridin-3-yl)-5-(hydroxymethyl)oxolane-3,4-diol
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| Synonyms |
1Deazaadenosine; 1 Deazaadenosine
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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 | 3.7559 mL | 18.7793 mL | 37.5587 mL | |
| 5 mM | 0.7512 mL | 3.7559 mL | 7.5117 mL | |
| 10 mM | 0.3756 mL | 1.8779 mL | 3.7559 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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