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| Targets |
cPrPMEDAP is an intermediate metabolite of GS-9219 and functions as a prodrug for the guanine nucleotide analog PMEG, which is the active antiviral and antiproliferative species. Once converted to PMEG, the active form is further phosphorylated to the triphosphate, which targets viral DNA polymerases and cellular DNA polymerases involved in replication, thereby inhibiting DNA synthesis.
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| ln Vitro |
cPrPMEDAP exhibits antiproliferative action in SiHa cells (i.e., HPV-transformed cervical cancer cell lines) at an EC50 of 290 nM [1]. As PMEG generates an active phosphorylated metabolite in cells, PMEG diphosphate (PMEG-DP), it potently inhibits nuclear DNA polymerases α, δ, and ʫ, hence inhibiting DNA synthesis and/or DNA repair and inhibiting the proliferation of numerous altered cell lines. PMEG has been shown to have antiproliferative properties in animal models; nevertheless, its effectiveness as an antiproliferative drug is constrained by its low cellular permeability and toxicity. While cPrPMEDAP is less hazardous in vivo and exhibits comparable antiproliferative properties in vitro, it is not as soluble in skin as PMEG and is negatively charged at physiological pH[1].
cPrPMEDAP exhibits antiproliferative action in vitro against SiHa cells (HPV-transformed cervical cancer cell lines) with an EC50 of 290 nM. It shows activity against lymphocyte regulation and immunosuppression. The compound is used to study antiviral mechanisms, purine-dependent signaling, and ADA-linked metabolic disorders. It is also useful for evaluating nucleotide-based therapies and immune cell proliferation and differentiation in research settings. |
| ln Vivo |
cPrPMEDAP has been studied for its in vivo activity as a prodrug of PMEG. It is an intermediate metabolite of GS-9219, which has been investigated for various therapeutic applications including antiviral and anticancer indications. The compound's activity provides a tool for dissecting ADA-linked metabolic disorders, evaluating nucleotide-based therapies, and probing immune cell proliferation and differentiation in living systems.
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| Enzyme Assay |
cPrPMEDAP can be tested in non-cellular enzyme assays. For in vitro studies, the compound is dissolved in an appropriate buffer (e.g., Tris-HCl, pH 7.4) to prepare a stock solution. The prodrug is incubated with cellular lysates or purified enzymes (e.g., adenylate deaminase) to study its conversion to active PMEG. Reactions are quenched with perchloric acid, and the resulting PMEG and phosphorylated metabolites are analyzed by HPLC or LC-MS to determine conversion rates.
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| Cell Assay |
For in vitro cellular experiments, cPrPMEDAP is tested on cell lines such as SiHa (HPV-transformed cervical carcinoma cells). Cells are seeded in 96-well plates at appropriate densities in culture medium (e.g., DMEM with 10% FBS). After 24 hours, cells are treated with various concentrations of cPrPMEDAP (e.g., 0.1 nM-100 uM) for 72 hours. Cell viability is measured using an MTT assay or CellTiter-Glo. EC50 values are calculated by nonlinear regression analysis of the dose-response curves.
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| Animal Protocol |
For in vivo animal experiments, cPrPMEDAP is typically administered to rodents via intravenous or oral routes as a prodrug (often as GS-9219, which metabolizes to cPrPMEDAP). Blood samples are collected at predetermined time points (0, 15, 30, 60, 120, 240 minutes) and plasma is analyzed by LC-MS/MS to quantify cPrPMEDAP and its active metabolite PMEG. Tissue samples (liver, kidney, spleen) may also be collected to assess distribution and accumulation of the nucleotide analog.
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| ADME/Pharmacokinetics |
As an intermediate metabolite of GS-9219, cPrPMEDAP shares the PK properties of the parent prodrug. GS-9219 is designed for oral administration and is rapidly converted to cPrPMEDAP, which is further metabolized to the active PMEG. cPrPMEDAP itself has poor permeability due to its negative charge at physiological pH, limiting its cellular entry without further modification. The active nucleotide analog PMEG has a long intracellular half-life due to slow efflux.
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| Toxicity/Toxicokinetics |
cPrPMEDAP has been evaluated in preclinical toxicology studies as part of GS-9219 development. The primary toxicity concerns for nucleotide analogs such as PMEG include dose-limiting nephrotoxicity, hepatotoxicity, and myelosuppression due to inhibition of host DNA polymerases. The compound has poor permeability into the skin, which may mitigate some dermal toxicities. Standard laboratory safety precautions apply. Not intended for human consumption.
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| References |
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| Additional Infomation |
cPrPMEDAP is not an approved drug but a research-use intermediate metabolite and prodrug. It has no approved therapeutic status. It is used in research to study lymphocyte regulation, immunosuppression, antiviral mechanisms, and purine-dependent signaling. It is also a valuable tool for dissecting ADA-linked metabolic disorders, evaluating nucleotide-based therapies, and probing immune cell proliferation and differentiation. The active form PMEG is a guanine nucleotide analog similar in mechanism to acyclovir and ganciclovir.
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| Molecular Formula |
C11H17N6O4P
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|---|---|
| Molecular Weight |
328.26428
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| Exact Mass |
328.104
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| CAS # |
182798-83-0
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| PubChem CID |
476082
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
-1.4
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
22
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| Complexity |
433
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1CC1NC2=C3C(=NC(=N2)N)N(C=N3)CCOCP(=O)(O)O
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| InChi Key |
PDHWTDJKKJYOGD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C11H17N6O4P/c12-11-15-9(14-7-1-2-7)8-10(16-11)17(5-13-8)3-4-21-6-22(18,19)20/h5,7H,1-4,6H2,(H2,18,19,20)(H3,12,14,15,16)
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| Chemical Name |
2-[2-amino-6-(cyclopropylamino)purin-9-yl]ethoxymethylphosphonic acid
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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: 10 mg/mL (30.46 mM)
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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 | 3.0464 mL | 15.2318 mL | 30.4637 mL | |
| 5 mM | 0.6093 mL | 3.0464 mL | 6.0927 mL | |
| 10 mM | 0.3046 mL | 1.5232 mL | 3.0464 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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