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| Targets |
Peldesine targets purine nucleoside phosphorylase (PNP), a key enzyme in the purine salvage pathway. PNP catalyzes the reversible phosphorolysis of purine nucleosides (inosine and guanosine) to their respective bases (hypoxanthine and guanine) and ribose-1-phosphate. By inhibiting PNP, Peldesine blocks the production of guanine nucleotides, leading to the accumulation of deoxyguanosine triphosphate (dGTP). This accumulation is toxic to T-cells, as it inhibits ribonucleotide reductase and DNA synthesis. The compound's selective inhibition of PNP makes it a potential therapeutic agent for T-cell-mediated diseases.
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| ln Vitro |
Peldesine (BCX 34; 0-50 μM; 72 hours; Jurkat cells) totally suppresses T cell proliferation in the presence of dGuo (10 μM) at doses below 10 μM. Peldesine, on the other hand, has no effect on B cell proliferation [1]. Peldesine (BCX 34) may influence late rather than early phases of T cell activation since it decreases T cell immunological responses in an IL-2-independent way [1]. With an IC50 of 0.57 μM, pendelasine also reduced the proliferation of human leukemia CCRF-CEM T cells, but not that of rat or mouse T cells, when deoxyguanosine was present. As much as 30 μM[3].
Peldesine exhibits potent in vitro activity as a PNP inhibitor. It has IC50 values of 36 nM, 5 nM, and 32 nM for human, rat, and mouse red blood cell PNP, respectively. The compound is a potent inhibitor of human CCRF-CEM T-cell proliferation. Its activity is assessed in enzyme assays measuring PNP-catalyzed phosphorolysis of inosine or guanosine. In cellular assays, the compound inhibits T-cell proliferation and induces apoptosis. These in vitro activities confirm its potential as an immunosuppressive and antiviral agent. |
| ln Vivo |
Rats have a 76% oral bioavailability of Peldesine. Peldesine can be taken orally and have the following effects: it can decrease rat RBC PNP activity in vitro (98% at 100 mg/kg in 3 hours), increase rat plasma inosine (2-fold at 30 mg/kg), and prevent mice from expressing isolated skin PNP. Medium (39% at 3 hours, 100 mg/kg) [3].
Peldesine has demonstrated in vivo activity in animal models. As an orally active PNP inhibitor, it can be administered conveniently. The compound has been studied for the treatment of T-cell-mediated diseases, including HIV infection. In vivo studies have shown that Peldesine reduces T-cell proliferation and may have antiviral effects. It has undergone Phase I clinical trials for HIV. Further studies are needed to fully characterize its therapeutic potential. |
| Enzyme Assay |
In vitro enzyme assays for Peldesine involve measuring its inhibition of purine nucleoside phosphorylase (PNP) activity. These assays typically use recombinant PNP and a substrate such as inosine or guanosine. The enzyme is incubated with the substrate and varying concentrations of Peldesine. The production of hypoxanthine or guanine is measured spectrophotometrically or by HPLC. The IC50 values are determined from dose-response curves. These assays confirm the compound's mechanism as a competitive and reversible PNP inhibitor.
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| Cell Assay |
Cell Proliferation Assay[1]
Cell Types: Jurkat Cell Tested Concentrations: 0 µM, 10 µM, 20 µM, 30 µM, 40 µM, 50 µM Incubation Duration: 72 hrs (hours) Experimental Results: Complete inhibition in the presence of 10 µM dCuo for T Cell lines. In vitro cellular assays for Peldesine are conducted in T-cell lines such as CCRF-CEM cells. Cells are treated with the compound at various concentrations, and cell proliferation is measured using MTT or CellTiter-Glo assays. T-cell activation and function are assessed by measuring cytokine production and surface marker expression. The compound's effects on purine nucleotide levels are measured by HPLC. These assays characterize the compound's immunosuppressive and antiviral activity. |
| Animal Protocol |
In vivo animal experiments with Peldesine are conducted in mouse models of T-cell-mediated diseases or HIV infection. The compound is administered orally at varying doses. T-cell proliferation and function are assessed in lymphoid tissues. Viral load is measured in HIV models. Pharmacodynamic studies are performed to confirm PNP inhibition and target engagement. These studies evaluate the compound's efficacy and mechanism of action in vivo.
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| ADME/Pharmacokinetics |
Peldesine is an orally active compound with favorable pharmacokinetic properties. It has good oral bioavailability. The compound has a molecular weight of 241.25 and is soluble in DMSO. Its half-life and tissue distribution have been characterized in preclinical studies. The compound is metabolized in the liver and excreted via biliary and renal routes. Its pharmacokinetic profile supports its use in clinical trials.
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| Toxicity/Toxicokinetics |
Peldesine has been evaluated for safety in preclinical and Phase I clinical studies. The compound is generally well-tolerated at therapeutic doses. As a PNP inhibitor, its toxicity profile may include immunosuppression and effects on purine metabolism. The compound is intended for research use and is not approved for human therapeutic use. Standard laboratory safety precautions should be followed when handling this compound.
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| References | |
| Additional Infomation |
Pedicine is a potent human CCRF-CEM T-cell proliferation inhibitor. It has completed a Phase I clinical trial for the treatment of human immunodeficiency virus (HIV) infection. Pedicine is a pyrimidine analog and purine nucleoside phosphorylase inhibitor with immunosuppressive and antitumor properties. Pedicine inhibits purine nucleoside phosphorylase (PNP), which plays a crucial role in T-cell proliferation by catalyzing the reversible phosphorylation of purine ribonucleosides and 2'-deoxyribonucleosides. Inhibition of PNP leads to the accumulation of dGTP, resulting in DNA synthesis failure. This drug can be used to treat T-cell-related autoimmune diseases, including psoriasis, rheumatoid arthritis, and Crohn's disease, as well as T-cell carcinoma.
Peldesine (BCX 34) is a potent, competitive, reversible, and orally active inhibitor of purine nucleoside phosphorylase (PNP). It has IC50 values of 36 nM, 5 nM, and 32 nM for human, rat, and mouse RBC PNP, respectively. The compound is a potent inhibitor of human CCRF-CEM T-cell proliferation. It has undergone Phase I trials for the treatment of HIV infections. Its selective inhibition of PNP makes it a potential therapeutic agent for T-cell-mediated diseases. |
| Molecular Formula |
C12H11N5O
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|---|---|
| Molecular Weight |
241.24864
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| Exact Mass |
241.096
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| CAS # |
133432-71-0
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| Related CAS # |
Peldesine dihydrochloride;2772702-10-8
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| PubChem CID |
135413525
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.57g/cm3
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| Boiling Point |
534ºC at 760mmHg
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| Flash Point |
276.7ºC
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| Vapour Pressure |
1.76E-11mmHg at 25°C
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| Index of Refraction |
1.794
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| LogP |
1.161
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
18
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| Complexity |
370
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
DOHVAKFYAHLCJP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C12H11N5O/c13-12-16-9-8(4-7-2-1-3-14-5-7)6-15-10(9)11(18)17-12/h1-3,5-6,15H,4H2,(H3,13,16,17,18)
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| Chemical Name |
2-amino-7-(pyridin-3-ylmethyl)-3,5-dihydropyrrolo[3,2-d]pyrimidin-4-one
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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) |
DMSO : ~200 mg/mL (~829.02 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (20.73 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 5 mg/mL (20.73 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 5 mg/mL (20.73 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.1451 mL | 20.7254 mL | 41.4508 mL | |
| 5 mM | 0.8290 mL | 4.1451 mL | 8.2902 mL | |
| 10 mM | 0.4145 mL | 2.0725 mL | 4.1451 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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