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Clevudine (L-FMAU; L FMAU; Levovir and Revovir) is a potent antiviral drug approved in South Korea and the Philippines for the treatment of hepatitis B (HBV) infections with EC50 0.1 μM in HepG2 2.2.15 cells as well as EBV. Numerous cell lines, such as MT2, CEM, H1, HepG2 2.2.15, and bone marrow progenitor cells, exhibit minimal cytotoxicity when exposed to clevodine exposure. In cells, clevudine is broken down into its monophosphate, then into its di- and triphosphates by cellular thymidine kinase and deoxycytidine kinase.
Physicochemical Properties
| Molecular Formula | C10H13FN2O5 | |
| Molecular Weight | 260.22 | |
| Exact Mass | 260.081 | |
| Elemental Analysis | C, 46.16; H, 5.04; F, 7.30; N, 10.77; O, 30.74 | |
| CAS # | 163252-36-6 | |
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| PubChem CID | 73115 | |
| Appearance | White to off-white solid powder | |
| Density | 1.55g/cm3 | |
| Melting Point | 184-185° | |
| Index of Refraction | 1.592 | |
| LogP | -0.9 | |
| Hydrogen Bond Donor Count | 3 | |
| Hydrogen Bond Acceptor Count | 6 | |
| Rotatable Bond Count | 2 | |
| Heavy Atom Count | 18 | |
| Complexity | 413 | |
| Defined Atom Stereocenter Count | 4 | |
| SMILES | F[C@@]1([H])[C@@]([H])(N2C(N([H])C(C(C([H])([H])[H])=C2[H])=O)=O)O[C@@]([H])(C([H])([H])O[H])[C@]1([H])O[H] |
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| InChi Key | GBBJCSTXCAQSSJ-XQXXSGGOSA-N | |
| InChi Code | InChI=1S/C10H13FN2O5/c1-4-2-13(10(17)12-8(4)16)9-6(11)7(15)5(3-14)18-9/h2,5-7,9,14-15H,3H2,1H3,(H,12,16,17)/t5-,6+,7-,9-/m0/s1 | |
| Chemical Name | 1-[(2S,3R,4S,5S)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione | |
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| HS Tariff Code | 2934.99.9001 | |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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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) |
Biological Activity
| Targets | RNA polymerase; DNA polymerase | ||
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| References |
[1]. Bioorg Med Chem Lett . 2002 Dec 2;12(23):3459-62. [2]. Antimicrob Agents Chemother . 2005 May;49(5):2044-9. [3]. Expert Rev Anti Infect Ther . 2006 Aug;4(4):549-61. [4]. J Biol Chem . 1995 Aug 11;270(32):19073-7. [5]. Antimicrob Agents Chemother . 2004 Jul;48(7):2683-92. |
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| Additional Infomation |
Clevudine is a pyrimidine 2'-deoxyribonucleoside. Clevudine is a synthetic pyrimidine analogue with activity against hepatitis B virus (HBV). Intracellularly, clevudine is phosphorylated to its active metabolites, clevudine monophosphate and triphosphate. The triphosphate metabolite competes with thymidine for incorporation into viral DNA, thereby causing DNA chain termination and inhibiting the function of HBV DNA polymerase (reverse transcriptase). Clevudine has a long half-life and shows significant reduction of covalently closed circular DNA (cccDNA), therefore the patient is less likely to have a relapse after treatment is discontinued. Drug Indication Investigated for use/treatment in hepatitis (viral, B). |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (9.61 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 25.0 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: ≥ 2.5 mg/mL (9.61 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 25.0 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (9.61 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.8429 mL | 19.2145 mL | 38.4290 mL | |
| 5 mM | 0.7686 mL | 3.8429 mL | 7.6858 mL | |
| 10 mM | 0.3843 mL | 1.9215 mL | 3.8429 mL |