Telbivudine (Epavudine; L-Thymidine; NV 02B; LDT 600; trade name:Tyzeka; Epavudine ) is a potent, and selective HBV (hepatitis B virus) reverse transcriptase inhibitor used primarily in the treatment of hepatitis B infection. It is an antiviral drug approved for the treatment of hepatitis B infection. Telbivudine is phosphorylated by intracellular thymidine kinases to the active triphosphate form, which has an intracellular half-life of 14 hours. Telbivudine 5′-triphosphate inhibits HBV DNA polymerase (reverse transcriptase) by competing with the natural substrate, dTTP.
理化性质和储存条件
| Molecular Weight (MW) | 242.23 |
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| Formula | C10H14N2O5 |
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| CAS No. | 3424-98-4 |
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| Storage | -20℃ for 3 years in powder form |
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| -80℃ for 2 years in solvent |
| Solubility (In vitro) | DMSO: 48 mg/mL (198.2 mM) |
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| Water: 48 mg/mL (198.2 mM) |
| Ethanol: 2 mg/mL warmed (8.3 mM) |
Other info
| Chemical Name: 1-((2S,4R,5S)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione
InChi Key: IQFYYKKMVGJFEH-CSMHCCOUSA-N
InChi Code: InChI=1S/C10H14N2O5/c1-5-3-12(10(16)11-9(5)15)8-2-6(14)7(4-13)17-8/h3,6-8,13-14H,2,4H2,1H3,(H,11,15,16)/t6-,7+,8+/m1/s1
SMILES Code: O=C1NC(C(C)=CN1[C@@H]2C[C@H]([C@H](CO)O2)O)=O |
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| Synonyms | Epavudine; L-Thymidine; NV 02B; NV-02B; NV02B; NV 02 B; NV-02-B; NV02-B; LDT 600; LD-T600; LDT600; Telbivudine; Tyzeka; Epavudine
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实验参考方法
| In Vitro | In vitro activity: Telbivudine shows potent, selective, and specific antiviral activity against HBV and other hepadna viruses. Telbivudine is phosphorylated by intracellular thymidine kinases to the active triphosphate form, which has an intracellular half-life of 14 hours. Telbivudine 5′-triphosphate inhibits HBV DNA polymerase (reverse transcriptase) by competing with the natural substrate, dTTP. Telbivudine significantly increases the production of tumour necrosis factor-alpha and interleukin-12 in MHV-3-induced macrophages. Telbivudine significantly elevates serum levels of interferon-gamma. Telbivudine treatment enhances the ability of T cells to undergo proliferation and secrete cytokines but does not affect cytotoxicity of infected hepatocytes. Telbivudine treatment suppresses programmed death ligand 1 expression on T cells. Telbivudine remains active as shown by respective fold-changes of 0.5 (N236T) and 1.0 (A181V and A194T). Telbivudine is not active against HBV strains bearing lamivudine mutations L180M/M204V/I but remains active against the M204V single mutant in vitro, potentially explaining the difference in resistance profiles between telbivudine and lamivudine. |
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| In Vivo | Telbivudine is an antiviral drug used in the treatment of hepatitis B infection. It is marketed by Swiss pharmaceutical company Novartis under the trade names Sebivo (Europe) and Tyzeka (United States). Clinical trials have shown it to be significantly more effective than lamivudine or adefovir, and less likely to cause resistance. Telbivudine is a synthetic thymidine nucleoside analogue, it is the L-isomer of thymidine. It is taken once daily. Telbivudine is a potent antiviral that provides effective and sustained viral suppression in patients with compensated CHB. In clinical trials, treatment outcomes were improved significantly more with telbivudine 600 mg once daily than with lamivudine 100 mg or adefovir 10 mg once daily, and telbivudine-treated patients had significantly less viral resistance than lamivudine-treated patients. Telbivudine is associated with a medium genetic barrier to resistance and, as patients with undetectable HBV DNA levels have significantly improved outcomes, it is recommended that HBV DNA levels are monitored at week 24 (and 6 monthly thereafter), with the addition of a nucleoside/nucleotide analogue without cross resistance (such as adefovir dipivoxil) if viraemia is present to reduce the risk of resistance (Roadmap concept). Telbivudine was generally well tolerated in clinical trials for periods of up to 4 years, and has a similar tolerability profile to that of lamivudine. |
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| References | Antimicrob Agents Chemother. 2008 Jul;52(7):2521-8; J Viral Hepat. 2010 Mar;17 Suppl 1:24-33. |
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