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Purity: ≥98%
Pradefovir mesylate (formerly known as Remofovir mesylate, ICN-2001-3 mesylate, MB-06866 mesylate, MB-6866 mesylate, ICN-20013 mesylate) is an RTI (reverse transcriptase) inhibitor that has the potential for the treatment of chronic HBV infection. It is also a good substrate for liver CYP3A4. Pradefovir is prodrug of adefovir that is designed to target liver. Pradefovir can be activated to PMEA (9-(2-phosphonylmethoxyethyl)adenine ) in human liver microsomes with with a Km of 60 μM, a maximum rate of metabolism of 228 pmol/min/mg protein, and an intrinsic clearance of about 359 ml/min.
| ln Vitro |
Pradefovir is a PMEA prodrug that is cyclic diester. It is one of the HepDirect prodrugs made to be selectively and potently activated by oxidative processes mediated by the liver-based enzyme CYP3A4. With a Km of 60 μM, a maximum metabolic rate of 228 pmol/min/mg protein, and an intrinsic clearance rate of around 359 L/min, pradefovir is transformed into PMEA in human liver microsomes [1].
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| ln Vivo |
For eight days, rats were given 300 mg/kg of prdefovir orally. The rats' body weight, liver weight, liver weight to body weight ratio, liver microsomal protein content, total CYP content, enzyme levels of CYP1A, CYP2B, and CYP3A activity, and apoprotein content of CYP1A1, CYP2B1/2, CYP3A1/2, and CYP4A1/3 were all unaffected, suggesting that prdefovir does not induce CYP in rats [1].
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| References | |
| Additional Infomation |
Pradefovir mesilate (previously known as MB-06886, Hepavir B and remofovir mesylate) is an orally administered small molecule compound that belongs to a novel series of phosphate and phosphonate prodrugs of adefovir. [Adefovir] (Hepsera) is an acyclic phosphonate analogue of adenine that is used to treat hepatitis B virus. As adefovir is poorly absorbed and associated with a high level of nephrotoxicity, pradefovir mesilate was designed to specifically target the liver and reduce risks to external tissue, especially the kidneys, while improving results of adefovir. Pradefovir is activated through oxidation that is mediated by cytochrome P-450 (CYP) 3A4, which is predominantly expressed in the liver. The novel prodrug is highly stable in both plasma and tissues and demonstrated potent preclinical and clinical anti-HBV activity. Pradefovir is undergoing phase II development for the treatment of chronic hepatitis B.
Pradefovir Mesylate is the mesylate salt form of pradefovir, a cyclodiester antiviral prodrug with specific activity against hepatitis B virus (HBV). Pradefovir is specifically metabolized in the liver by hepatic enzymes, mainly by CYP4503A4, to adefovir. In turn, adefovir is phosphorylated by cellular kinases to its activated form adevofir diphosphate. By competing with the natural substrate dATP, the diphosphate form is incorporated into viral DNA and inhibits RNA-dependent DNA polymerase. This causes DNA chain termination and eventually results in an inhibition of HBV replication. See also: Pradefovir (annotation moved to). Drug Indication Investigated for use as a prodrug for Hepsera in treating hepatitis (viral, B). Mechanism of Action Pradefovir is activated through oxidation that is mediated by cytochrome P-450 (CYP) 3A4, which is predominantly expressed in the liver. In this way, it allows for increased Hepsera concentrations selectively in the liver. Pharmacodynamics Pradefovir is activated through oxidation that is mediated by cytochrome P-450 (CYP) 3A4, which is predominantly expressed in the liver. Accordingly, pradefovir allows Hepsera to be concentrated in the liver, while maintaining lower concentration levels in other tissue. The novel prodrug is an orally administered small molecule compound that belongs to a novel series of phosphate and phosphonate drugs. It is highly stable in both plasma and tissues. |
| Molecular Formula |
C13H23CLN5O7PS
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| Molecular Weight |
519.90
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| Exact Mass |
519.074
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| CAS # |
625095-61-6
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| Related CAS # |
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| PubChem CID |
9604653
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| Appearance |
White to off-white solid powder
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| LogP |
4.573
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
33
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| Complexity |
668
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CS(=O)(=O)O.C1CO[P@@](=O)(O[C@@H]1C2=CC(=CC=C2)Cl)COCCN3C=NC4=C(N=CN=C43)N
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| InChi Key |
JXQUAHHUSMJUFV-HZPZRMRQSA-N
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| InChi Code |
InChI=1S/C17H19ClN5O4P.CH4O3S/c18-13-3-1-2-12(8-13)14-4-6-26-28(24,27-14)11-25-7-5-23-10-22-15-16(19)20-9-21-17(15)23;1-5(2,3)4/h1-3,8-10,14H,4-7,11H2,(H2,19,20,21);1H3,(H,2,3,4)/t14-,28+;/m0./s1
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| Chemical Name |
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| Synonyms |
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 100 mg/mL (192.34 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9234 mL | 9.6172 mL | 19.2345 mL | |
| 5 mM | 0.3847 mL | 1.9234 mL | 3.8469 mL | |
| 10 mM | 0.1923 mL | 0.9617 mL | 1.9234 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.
Ketoconazole inhibition of conversion of pradefovir to PMEA in human liver microsomes as a percentage of the control activity (mean;n= 2) versus the concentration of pradefovir.Antimicrob Agents Chemother.2006 Sep;50(9):2926-31. |
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Determination ofKi(slope versus [I] plot) for ketoconazole on conversion of pradefovir to PMEA (mean;n= 2).Antimicrob Agents Chemother.2006 Sep;50(9):2926-31. |
MAb 3A4 inhibition of conversion of pradefovir to PMEA (mean;n= 2) in human liver microsomes.Antimicrob Agents Chemother.2006 Sep;50(9):2926-31. |
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